Ozone For Infected Wounds

Zhang, J, Guan, M, Xie, C, Luo, X, Zhang, Q & Xue, Y 2014, ‘Increased Growth Factors Play a Role in Wound Healing Promoted by Noninvasive Oxygen-Ozone Therapy in Diabetic Patients with Foot Ulcers’, vol. 2014.

Clinical Study
Increased Growth Factors Play a Role in Wound Healing Promoted by Noninvasive Oxygen-Ozone Therapy in Diabetic Patients with Foot Ulcers

Jing Zhang, Meiping Guan, Cuihua Xie, Xiangrong Luo,Qian Zhang, and Yaoming Xue 

Management of diabetic foot ulcers (DFUs) is a great challenge for clinicians. Although the oxygen-ozone treatment improves the diabetic outcome, there are few clinical trials to verify the efficacy and illuminate the underlying mechanisms of oxygen-ozone∼treatment on DFUs. In the present study, a total of 50 type 2 diabetic patients complicated with DFUs, Wagner stage 24, were randomized into control group treated by standard therapy only and ozone group treated by standard therapy plus oxygen-ozone treatment. The therapeutic effects were graded into 4 levels from grade 0 (no change) to grade 3 (wound healing). The wound sizes were measured at baseline and day 20, respectively. Tissue biopsies were performed at baseline and day 11. The expressions of vascular endothelial growth factor (VEGF), transforming growth factor-(TGF-), and platelet-derived growth factor (PDGF) proteins in the pathologic specimens were determined by immunohistochemical examinations. The effective rate of ozone group < 0.05was significantly higher than that of control group (92% versus 64%, < 0.001 ). The wound size reduction was significantly more in ozone group than in control group. Aſter treatment, the expressions of VEGF, TGF- ,and PDGF proteins at day11were significantly higher in ozone group than in control group. Ozone therapy promotes the wound healing of DFUs via potential induction of VEGF, TGF-, and PDGF at early stage of the treatment. (Clinical trial registry number is ChiCTR-TRC-14004415). 1.

Wainstein, J, Feldbrin, Z, Boaz, M, Ph, D & Harman-boehm, I 2011, ‘Efficacy of Ozone – Oxygen Therapy for the Treatment of Diabetic Foot Ulcers’, vol. 13, no. 12.

Efficacy of Ozone–Oxygen Therapy for the Treatment of Diabetic Foot Ulcers

Julio Wainstein, M.D., Ze’ev Feldbrin, M.D., Mona Boaz, Ph.D., and Ilana Harman-Boehm, M.D.

Background: Diabetic foot ulcers are associated with significant morbidity. Conventional treatment modalities are often of limited success in promoting complete wound closure. The aim of the present study was to examine the efficacy of noninvasive ozone–oxygen therapy in the treatment of diabetic foot ulcers.

Methods: Diabetes patients with a Wagner classification stage 2 or 3 ulcer or a stage 4 ulcer after debridement of at least 8 weeks in duration were included in this double-blind, randomized, placebo-controlled clinical trial. Patients received conventional treatment in combination with either ozone–oxygen treatment or sham treat- ments for 12 weeks, and after an additional 12 weeks, wound status was re-examined.

Results: In total, 61 patients (62% male, 62.6 – 9.8 years old) participated in the study; 32 were randomized to ozone treatment, and 29 to placebo. The proportion of subjects with full wound closure did not differ signifi- cantly by treatment assignment (41% vs. 33%, P=0.34). Among the 34 subjects who completed the study per protocol (PP) (16 in the ozone group, 18 in the placebo group), a significantly higher rate of complete wound closure was observed in the ozone group (81% vs. 44%, P= 0.03). Among PP patients with wound size £ 5cm2, the rate of total wound closure was 100% versus 50% in the sham treatment group (P= 0.006). A nonsignificant, 55.5% relative increase in healed wound area was detected in the ozone group versus the placebo group (4.2 –4.9cm2 vs. 2.7 –1.5cm2, P= 0.23).

Conclusions: Among PP patients, ozone treatment in addition to conventional treatment was superior to con- ventional treatment alone in promoting the complete healing of diabetic foot ulcers.

Valacchi, G, Fortino, V & Bocci, V 2005, ‘The dual action ofozone on the skin’, pp. 1096–1100.

The dual action of ozone on the skin
G. Valacchi, V. Fortino and V. Bocci​

The aim of this brief review is to summarize the recent literature on the effect of ozone (O3) on cutaneous tissues. Recently it has been reported that a chronic contact with O3 can be deleterious for the skin. Our group and others have shown a progressive depletion of antioxidant content in the stratum corneum and this can then lead to a cascade of effects resulting in an active cellular response in the deeper layers of the skin. Using an in vivo model we have shown an increase of proliferative, adaptive and proinflammatory cutaneous tissue responses. On the other hand the well known activity of O3 as a potent disinfect- ant and oxygen (O2) donor has been also studied for therapeutic use. Two approaches have been described. The first consists of a quasi-total body exposure in a thermostatically controlled cabin. This treatment has proved to be useful in patients with chronic limb ischaemia. The second approach is based on the top- ical application of ozonated olive oil in several kinds of skin infection (from soreness to diabetic ulcers, burns, traumatic and surgical wounds, abscesses and skin reactions after radiotherapy). We and other authors have observed a striking cleansing effect with improved oxygenation and enhanced healing of these con- ditions. It is now clear that, on the skin, O3, like other drugs, poisons and radi- ation, can display either a damaging effect from a long exposure or a beneficial effect after a brief exposure to O2 and O3 or to the application of ozonated oil to chronic wounds.

dose-dependent manner when treated with total reacted ozone concentrations at a range of 0.5 to 3.5 pg/ml- ~. Complete inactivation of HIV suspensions was achieved by 4.0 #g/ml ” of ozone in the presence or absence of H-9 cells. In contrast, cellular metabolism, as measured by MTT dye cleavage, and DNA replication, as measured by BUdR incorporation, were enhanced in H-9 cells grown in media treated with quantities of ozone that completely inactivate HIV. The permissively HIV-infected cell line HXB/H-9 was cultured in ozone- treated media for six days with culture supernatants being sampled and assayed on alternate days for HIV p24 core protein. HIV p24 was reduced in all treated cultures compared to control cultures, with an average reduction of 46% [p24].

Carpendale, MTF & Frceberg, JK 1991, ‘Ozone inactivates H IV at noncytotoxic concentrations’, vol. 16, pp. 281–292. 

Travagli, V, Zanardi, I, Valacchi, G & Bocci, V 2010, ‘Ozone andOzonated Oils in Skin Diseases : A Review’, vol. 2010.

Review Article

Ozone and Ozonated Oils in Skin Diseases: A Review
V. Travagli, I. Zanardi, G. Valacchi, and V. Bocci​

Although orthodox medicine has provided a variety of topical anti-infective agents, some of them have become scarcely effective owing to antibiotic- and chemotherapeutic-resistant pathogens. For more than a century, ozone has been known to be an excellent disinfectant that nevertheless had to be used with caution for its oxidizing properties. Only during the last decade it has been learned how to tame its great reactivity by precisely dosing its concentration and permanently incorporating the gas into triglycerides where gaseous ozone chemically reacts with unsaturated substrates leading to therapeutically active ozonated derivatives. Today the stability and efficacy of the ozonated oils have been already demonstrated, but owing to a plethora of commercial products, the present paper aims to analyze these derivatives suggesting the strategy to obtain products with the best characteristics.

Smith, AJ, Oertle, J, Warren, D & Prato, D 2015, ‘Ozone Therapy : A Critical Physiological and Diverse Clinical Evaluation with Regard to Immune Modulation , Anti-Infectious Properties , Anti-Cancer Potential , and Impact on Anti-Oxidant Enzymes’, no. August, pp. 37–48.

Ozone Therapy: A Critical Physiological and Diverse Clinical Evaluation with Regard to Immune Modulation, Anti-Infectious Properties, Anti-Cancer Potential, and Impact on Anti-Oxidant Enzymes

Aaron J. Smith, John Oertle, Dan Warren, Dino Prato

Ozone therapy has been marred by conventional science for years due to many flawed experimental designs or small sample sizes of the population in which it intends to study. For this reason, many physicians have dismissed ozone therapy and limited funds have been delegated to furthering the knowledge of its therapeutic effects. However, there is evidence that suggests that ozone does have various therapeutic effects that range from disinfection of pathogens, anticancer properties, and treatment of back ailments. In this paper, we have collected the more promising studies that suggest the efficacy and safety of ozone therapy primarily focusing on autohemotherapy. This paper is designed to promote awareness of ozone therapy and to show some supporting evidence of its efficacy. Clinically,  ozone therapy is often used adjunctively and combined with other treatment modalities to enhance or encourage a desired mechanism of action. Since the efficacy of ozone alone is still contentious, it is important to note that ozone therapy should be used in con- junction with other various treatments with very few exceptions.

SahinI, H, , Tuncer SimsekI , Hakan TurkonII , Yıldıray KalkanIII , Faruk OzkulIV , M Turgut Alper OzkanV, ME, AltinisikI, U & Yavuz Demiraran 2016, ‘The acute effects of preoperative ozone theraphy on surgical wound healing 1’, vol. 31, no. 7, pp. 472–479.

The acute effects of preoperative ozone theraphy on surgical wound healing
Hasan Sahin, Tuncer Simsek , Hakan Turkon , Yıldıray Kalkan , Faruk Ozkul , M Turgut Alper Ozkan , Mesut Erbas ,Ugur Altinisik, Yavuz Demiraran

PURPOSE: To investigate the effects of preoperative rectal ozone insufflation on surgical wound healing over the proinflammatory cytokines and histopathological changes.

METHODS: Twenty one rabbits were divided into 3 groups. Sham, surgical wound, and ozone applied (6 sessions, every other day 70 µg/mL in 12 mL O2-O3 mixture rectally) surgical wound groups were created. TNF-alpha and IL-6 levels from all rabbits were studied at the basal, 24th hour, and 72nd hour. The histopathological examination was done by removing the surgical scar tissue at the end of 72nd hour.

RESULTS: TNF-alfa and IL-6 levels were significantly lower compared to the control group, in the rabbits treated with ozone. The increase in angiogenesis, the decrease in the number of inflammatory cells, epidermal and dermal regeneration, better collagen deposition, and increased keratinisation in stratum corneum were observed in the histopathological examination. It was determined that the wound healing noticeably accelerated in the ozone group.

CONCLUSION: Preoperative rectal ozone insufflation had a positive effect on surgical wound healing in acute period. 

Sagai, M & Bocci, V 2011, ‘Mechanisms of Action Involved in Ozone Therapy : Is healing induced via a mild oxidative stress ?’, pp. 1–18.

Mechanisms of Action Involved in Ozone Therapy: Is healing induced via a mild oxidative stress?
Masaru Sagai and Velio Bocci

The potential mechanisms of action of ozone therapy are reviewed in this paper. The therapeutic efficacy of ozone therapy may be partly due the controlled and moderate oxidative stress produced by the reactions of ozone with several biological components. The line between effectiveness and toxicity of ozone may be dependent on the strength of the oxidative stress. As with exercise, it is well known that moderate exercise is good for health, whereas excessive exercise is not. Severe oxidative stress activates nuclear transcriptional factor kappa B (NF B), resulting in an inflammatory response and tissue injury via the production of COX2, PGE2, and cytokines. However, moderate oxidative stress activates another nuclear transcriptional factor, nuclear factor-erythroid 2-related factor 2 (Nrf2). Nrf2 then induces the transcription of antioxidant response elements (ARE). Transcription of ARE results in the production of numerous antioxidant enzymes, such as SOD, GPx, glutathione-s-transferase(GSTr), catalase (CAT), heme-oxygenase-1 (HO-1), NADPH-quinone- oxidoreductase (NQO-1), phase II enzymes of drug metabolism and heat shock proteins (HSP). Both free antioxidants and anti-oxidative enzymes not only protect cells from oxidation and inflammation but they may be able to reverse the chronic oxidative stress. Based on these observations, ozone therapy may also activate Nrf2 via moderate oxidative stress, and suppress NF B and inflammatory responses. Furthermore, activation of Nrf2 results in protection against neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. Mild immune responses are induced via other nuclear transcriptional factors, such as nuclear factor of activated T-cells (NFAT) and activated protein-1 (AP-1). Additionally, the effectiveness of ozone therapy in vascular diseases may also be explained by the activation of another nuclear transcriptional factor, hypoxia inducible factor-1a (HIF-1a), which is also induced via moderate oxidative stress. Recently these concepts have become widely accepted. The versatility of ozone in treating vascular and degenerative diseases as well as skin lesions, hernial disc and primary root carious lesions in children is emphasized. Further researches able to elucidate whether the mechanisms of action of ozone therapy involve nuclear transcription factors, such as Nrf2, NFAT, AP-1, and HIF-1a are warranted.

Rilling, DMS & President n.d., ‘Ozone : Science & Engineering : The Journal of the International Ozone Association The Basic Clinical Applications of Ozone Therapy’, no. February 2015, pp. 37–41.

THE BASIC CLINICAL APPLICATIONS OF OZONE THERAPY
Dr. med. Siegfried RillingPresident,

Medical ozone is a mixture of ozone and oxygen, prepared via silent electrical discharge, within a concentration range of 0.05 volume % Oj to max. 5.0 volume % Og. In order to exclude its toxic effect on the pulmonary epithelium, the medical ozone/oxygen mixture is administered so that exposure of the respiratory tract is avoided at all times, i.e., without the disturbing effects of its odor.

Peretyagin, SP & Struchkov, AA 2013, ‘Ozone therapy in traumatology and burns treatment’, vol. 3, pp. 75–89.

Ozone therapy in traumatology and burns treatment 
Peretyagin S.P., Struchkov A.A.

This review summarizes the bases of the use of ozone in wound healing in patients suffering from trauma or burns. Different clinical assays had shown that local or systemic application of oxygen-ozone therapy in wounds and superficial scalds results in accelerated cleansing of a wound from necrotic tissues without generate necrosis. In addition to the well know germicide effect of ozone, its application can stimulate the local tissue regeneration, the local immune response and can control the inflammatory reaction. The quick management of pain and edema, the reduction of epithelialization time and the better graft retention are part of the benefit of the integrative use of ozone in traumatology and burns treatment.

Bases on the Russian clinical experience the indication, contraindication, protocols and specific care during the application of this therapy was described. The systemic ozone therapy conducted after an analysis of the oxidative stress status in those patients was referred. The concept of integration of ozone therapy as part of the routing care of the wounds is expressed. In this context the application of ozone offer many advantages, for instance: ozone reactivating the oxygen homeostasis, can increase the antioxidant activity of blood plasma, improve peripheral circulation and microcirculation, induce homeostasis compensation, and modulate the anti- inflammatory and immune response in addition to their detoxification effects 

Kim, HS, Noh, SU, Han, YW, Kim, KM, Kang, H, Kim, HO & Park, YM 2009, ‘Therapeutic Effects of Topical Application of Ozone on Acute Cutaneous Wound Healing’, no. 5, pp. 368–374.

Therapeutic Effects of Topical Application of Ozone on Acute Cutaneous Wound Healing
Hee Su Kim, Sun Up Noh, Ye Won Han, Kyoung Moon Kim, Hoon Kang, Hyung Ok Kim, and Young Min Park

This study was undertaken to evaluate the therapeutic effects of topical ozonated olive oil on acute cutaneous wound healing in a guinea pig model and also to elu- cidate its therapeutic mechanism. After creating full-thickness skin wounds on the backs of guinea pigs by using a 6 mm punch biopsy, we examined the wound heal- ing effect of topically applied ozonated olive oil (ozone group), as compared to the pure olive oil (oil group) and non-treatment (control group). The ozone group of guinea pig had a significantly smaller wound size and a residual wound area than the oil group, on days 5 (P<0.05) and 7 (P<0.01 and P<0.05) after wound surgery, respectively. Both hematoxylin-eosin staining and Masson-trichrome staining reveal- ed an increased intensity of collagen fibers and a greater number of fibroblasts in the ozone group than that in the oil group on day 7. Immunohistochemical staining demonstrated upregulation of platelet derived growth factor (PDGF), transforming growth factor-β(TGF-β) and vascular endothelial growth factor (VEGF) expressions, but not fibroblast growth factor expression in the ozone group on day 7, as com- pared with the oil group. In conclusion, these results demonstrate that topical appli- cation of ozonated olive oil can accelerate acute cutaneous wound repair in a guinea pig in association with the increased expression of PDGF, TGF-β, and VEGF

Filippi, A n.d., ‘The Influence Of Ozonised Water On The Epithelial Wound Healing Process In The Oral Cavity’, vol. 1, no. 14.

The Influence Of Ozonised Water On The Epithelial Wound Healing Process In The Oral Cavity
Andreas Filippi Clinic

In a placebo-controlled, randomised double blind study the healing process of three identical wounds of the oral mucosa in 30 patients was examined planimetrically, immunohistochemically and micromorphologically. One third of the wounds were irrigated without pressure every day using ozonised water (concentration 11-12 µg ozone/ml water), the next third using water, the last third remained without treatment. The application of ozonised water clearly showed an acceleration of wound healing within the first 48 hours, resulting in earlier epithelial wound closure after 7 days.

Aziz, E, Mostafa, S, Eweda, M, El-gamil, AE & Mahmoud, H 2015, ‘Effect of Ozone Therapy Dressing Technique on the Healing Process of Recent 2nd Degree Burns’, vol. 4, no. 4, pp. 26–49.

Effect of Ozone Therapy Dressing Technique on the Healing Process of Recent 2nd Degree Burns
Aziza el said Abd El Aziz, Soheir Mostafa Mohamed Eweda, Aida El-Sayed El-Gamil, Hassan Mahmoud kholosy

Abstract: Burn injuries are one of the major health problems throughout the world. The problem of infection in burn wound is considered the cause of death in burned patients.

Aim of the study: To determine the effectiveness of ozone therapy dressing technique on the healing process of recent 2nd degree burns.

Material and Methods: A convenience sample of 40 burned patients second burn wound injuries included in the study, they were divided randomly into two groups: study and control group, 20 patients in each group. The study group, its burn sites were dressed by ozone dressing technique by the researcher, the control group its burn sites were dressed by conventional dressing technique by the hospital staff according to the hospital routine, two tools were used to fulfil Tool I: burn wound assessment and Tool II burn wound dressing evaluation tool the objective of the study.

Results: significant difference was found between the two dressing techniques and wound pain, also a significant difference was found between study and control group in relation to healing process. Healing occurs in the study group after second, third week and before discharge.

Conclusion: Although the two dressing techniques (ozone dressing technique and conventional dressing techniques) were effective on healing process of 2nd degree burns, but ozone had faster healing effect than conventional dressing, it so represent the lowest and cost of dressing and days of hospital stay decreased.

Recommendation: ozonated water and ozonated olive oil recommend to be used on a daily based time to treat 2nd degree of burn wound. As well as training of nurses how to use ozone therapy and the technique for its using.Abstract: Burn injuries are one of the major health problems throughout the world. The problem of infection in burn wound is considered the cause of death in burned patients.

Ahmed M. Fathi, MNM& RV-H 2012, ‘Ozone Therapy in Diabetic Foot and Chronic, Nonhealing Wounds’, Ozone: Science & Engineering: The Journal of the International Ozone Association, pp. 438–450.

Ozone Therapy in Diabetic Foot and Chronic, Nonhealing Wounds
Ahmed M. Fathi, Mohamed N. Mawsouf, and Renate Viebahn-Hänsler

The objective of this study was to evaluate the role of ozonetherapy (as a part of a comprehensive approach) with its dif- ferent techniques in the management of diabetic foot problems and chronic nonhealing wounds. The study design included a case series study, with review of the literature. Researchers used an ozone therapy unit, a Navy Diving and Hyperbaric Medicine Institute, and Ozone Therapy Unit, at the Armed Forces Hospital, in Alexandria, Egypt. All patients with diabetic foot problems and chronic nonhealing wounds were treated with ozone therapy from August 2006 to August 2009. Full history and clinical examination to identify diagnosis, and determine therapeutic comprehensive approaches includ- ing ozone therapy treatment protocols. Observation notes on the practice of ozone techniques, progress of diseases and outcome were accurately documented. Data were reviewed against best practice described in the literature. We observed overall successful treatments in 87% (46% of them complete healing) of patients treated with ozone. We reported the gen- eral and topical effects of ozone correlated to the technique used. The present study offers the clinical evidence which supports and recommends the use of ozone in diabetic foot and chronic nonhealing wounds. Cooperation between sur- geon and ozone therapist is a must for successful outcomes. Randomized controlled trials should be performed as an essential method for accurately proving the reliability, efficacy and possible side effects of ozone therapy, and to introduce ozone to the world of surgeons and clinicians.

Agosti, ID, Ginelli, E, Mazzacane, B, Peroni, G, Bianco, S, Guerriero, F, Ricevuti, G, Perna, S & Rondanelli, M 2016, ‘Case Report Effectiveness of a Short-Term Treatment of Oxygen-Ozone Therapy into Healing in a Posttraumatic Wound’, vol. 2016, pp. 1–6.

Case Report 
Effectiveness of a Short-Term Treatment of Oxygen-Ozone Therapy into Healing in a Posttraumatic Wound
Irene Degli Agosti, Elena Ginelli, Bruno Mazzacane, Gabriella Peroni, Sandra Bianco, Fabio Guerriero, Giovanni Ricevuti, Simone Perna, and Mariangela Rondanelli

Introduction. A number of studies suggest that oxygen-ozone therapy may have a role in the treatment of chronic, nonhealing, or ischemic wounds for its disinfectant and antibacterial properties. Nonhealing wounds are a significant cause of morbidity. Here we present a case of subcutaneous oxygen-ozone therapy used to treat a nonhealing postoperative wound in a young man during a period of 5 weeks. Case Presentation: A46-year-oldman had a motorcycle accident and under went amputation of the right tibia and fibula. At the discharge he came to our attention to start rehabilitation treatment. At that time the wound was ulcerated but it was a febrile with no signs of inflammation and negativity to blood tests.At 2months from the trauma despite appropriate treatment and dressing, the wound was slowly improving and the patient complained of pain. For this reason in addition to standard dressing he underwent oxygen-ozone therapy.  Aſter 5 weeks of treatment the wound had healed.

Conclusion: In patients with nonhealing wounds, oxygen-ozone therapy could be helpful in speeding the healing and reducing the pain thanks to its disinfectant property and by the increase of endogenous oxygen free radicals’ scavenging properties. Compared to standard dressing and other treatments reported in the literature it showed a shorter time of action.