Ozone Abstracts 1

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Does ozone therapy normalize the cellular redox balance? Implications for therapy of human immunodeficiency virus infection and several other diseases.
            (Bocci, 1996) Download
The role of ozone on earth is controversial, as in the stratosphere it is protective against excessive ultra violet irradiation, and in the troposphere it is toxic for animals and plants. The effectiveness of ozone against pathogens is well recognized and ozone appears to be the best agent for sterilization of water. In spite of this, the use of ozone in medicine has been overlooked or despised, mostly because it has been either misused or used without appropriate controls. Studies carried out in our laboratory have revealed that ozone can display relevant biological effects and that, having defined its therapeutic index, can become an important and reliable drug for the treatment of several diseases. An exciting new aspect is that ozone, being a strong oxidizer, can stimulate the increase of cellular anti-oxidant enzymes, eventually inhibiting the oxidative stress.

Ozonation of human blood induces a remarkable upregulation of heme oxygenase-1 and heat stress protein-70.
            (Bocci et al., 2007) Download
Heme oxygenase-I (HO-1) has emerged as one of the most protective enzymes and its pleiotropic activities have been demonstrated in a variety of human pathologies. Unpublished observations have shown that HO-1 is induced after the infusion of ozonated blood into the respective donors, and many other experimental observations have demonstrated the efficacy of oxidizing agents. It appeared worthwhile to evaluate whether we could better define the activity of potential inducers such as hydrogen peroxide and ozonated human plasma. Human vascular endothelial cells at confluence were challenged with different concentrations of these inducers and the simultaneous production of nitric oxide (NO); and HO-1 was measured by either measuring nitrite, or bilirubin formation, or/and the immune reactivity of the protein by Western blot using a rabbit antihuman HO-1 and Hsp-70. The results show that production of both NO and HO-1 is fairly dose dependent but is particularly elevated using human plasma after transient exposure to a medium ozone concentration. At this concentration, there is also induction of Hsp-70. The results clarify another positive effect achievable by the use of ozone therapy.


The ozone paradox: ozone is a strong oxidant as well as a medical drug.
            (Bocci et al., 2009) Download
After five decades characterized by empiricism and several pitfalls, some of the basic mechanisms of action of ozone in pulmonary toxicology and in medicine have been clarified. The present knowledge allows to understand the prolonged inhalation of ozone can be very deleterious first for the lungs and successively for the whole organism. On the other hand, a small ozone dose well calibrated against the potent antioxidant capacity of blood can trigger several useful biochemical mechanisms and reactivate the antioxidant system. In detail, firstly ex vivo and second during the infusion of ozonated blood into the donor, the ozone therapy approach involves blood cells and the endothelium, which by transferring the ozone messengers to billions of cells will generate a therapeutic effect. Thus, in spite of a common prejudice, single ozone doses can be therapeutically used in selected human diseases without any toxicity or side effects. Moreover, the versatility and amplitude of beneficial effect of ozone applications have become evident in orthopedics, cutaneous, and mucosal infections as well as in dentistry.

Diabetes and chronic oxidative stress. A perspective based on the possible usefulness of ozone therapy.
            (Bocci et al., 2011b) Download
It is now well established that hyperglycemia, present in both type 1 and type 2 diabetes, causes a variety of biochemical derangements leading to a diffused vascular damage responsible for several pathologic manifestations. Although preclinical and clinical studies have been performed by an unreliable administration route, the correct approach of oxygen-ozonetherapy may break a vicious circle. Messengers, released by a precise interaction ex vivo of the patient's blood with an equivalent calculated dose of ozone (0.42-0.84 mM), react with a variety of cells after blood infusion and restore a number of functions went astray. This paper aims to open a debate on this new therapy for improving the prognosis of diabetes.

Oxygen/ozone as a medical gas mixture. A critical evaluation of the various methods clarifies positive and negative aspects.
            (Bocci et al., 2011a) Download
Besides oxygen, several other gases such as NO, CO, H2, H2S, Xe and O3 have come to age over the past few years. With regards to O3, its mechanisms of action in medicine have been clarified during the last two decades so that now a comprehensive framework for understanding and recommending ozone therapy in various pathologies is available. O3 used within the determined therapeutic window is absolutely safe and more effective than golden standard medications in numerous pathologies, like vascular diseases. However, ozone therapy is mostly in practitioners' hands and some recent developments for increasing cost effectiveness and speed of treatment are neither standardized, nor evaluated toxicologically. Hence, the aim of this article is to emphasize the need to objectively assess the pros and cons of oxygen/ozone as a medical gas mixture in the hope that ozone therapy will be accepted by orthodox medicine in the near future.

Ozone acting on human blood yields a hormetic dose-response relationship.
            (Bocci et al., 2011c) Download
The aim of this paper is to analyze why ozone can be medically useful when it dissolves in blood or in other biological fluids. In reviewing a number of clinical studies performed in Peripheral Arterial Diseases (PAD) during the last decades, it has been possible to confirm the long-held view that the inverted U-shaped curve, typical of the hormesis concept, is suitable to represent the therapeutic activity exerted by the so-called ozonated autohemotherapy. The quantitative and qualitative aspects of human blood ozonation have been also critically reviewed in regard to the biological, therapeutic and safety of ozone. It is hoped that this gas, although toxic for the pulmonary system during prolonged inhalation, will be soon recognized as a useful agent in oxidative-stress related diseases, joining other medical gases recently thought to be of therapeutic importance. Finally, the elucidation of the mechanisms of action of ozone as well as the obtained results in PAD may encourage clinical scientists to evaluate ozone therapy in vascular diseases in comparison to the current therapies.

Ozone Therapy for Tumor Oxygenation: a Pilot Study.
            (Clavo et al., 2004b) Download
Tumor hypoxia is an adverse factor for chemotherapy and radiotherapy. Ozone therapy is a non-conventional form of medicine that has been used successfully in the treatment of ischemic disorders. This prospective study was designed to assess the effect of ozone therapy on tumor oxygenation. Eighteen subjects were recruited for the study. Systemic ozone therapy was administered by autohemotransfusion on three alternate days over one week. Tumor oxygenation levels were measured using polarographic needle probes before and after the first and the third ozone therapy session. Overall, no statistically significant change was observed in the tumor oxygenation in the 18 patients. However, a significant decrease was observed in hypoxic values </=10 and </=5 mmHg of pO(2). When individually assessed, a significant and inverse non-linear correlation was observed between increase in oxygenation and the initial tumor pO(2) values at each measuring time-point, thus indicating that the more poorly-oxygenated tumors benefited most (rho = -0.725; P = 0.001). Additionally, the effect of ozone therapy was found to be lower in patients with higher hemoglobin concentrations (rho = -0.531; P < 0.034). Despite being administered over a very short period, ozone therapy improved oxygenation in the most hypoxic tumors. Ozone therapy as adjuvant in chemo-radiotherapy warrants further research.

Ozone Therapy on Cerebral Blood Flow: A Preliminary Report.
            (Clavo et al., 2004a) Download
Ozone therapy is currently being used in the treatment of ischemic disorders, but the underlying mechanisms that result in successful treatment are not well known. This study assesses the effect of ozone therapy on the blood flow in the middle cerebral and common carotid arteries. Seven subjects were recruited for the therapy that was performed by transfusing ozone-enriched autologous blood on 3 alternate days over 1 week. Blood flow quantification in the common carotid artery (n = 14) was performed using color Doppler. Systolic and diastolic velocities in the middle cerebral artery (n = 14) were estimated using transcranial Doppler. Ultrasound assessments were conducted at the following three time points: 1) basal (before ozone therapy), 2) after session #3 and 3) 1 week after session #3. The common carotid blood flow had increased by 75% in relation to the baseline after session #3 (P < 0.001) and by 29% 1 week later (P = 0.039). In the middle cerebral artery, the systolic velocity had increased by 22% after session #3 (P = 0.001) and by 15% 1 week later (P = 0.035), whereas the diastolic velocity had increased by 33% after session #3 (P < 0.001) and by 18% 1 week later (P = 0.023). This preliminary Doppler study supports the clinical experience of achieving improvement by using ozone therapy in peripheral ischemic syndromes. Its potential use as a complementary treatment in cerebral low perfusion syndromes merits further clinical evaluation.

Brain ischemia and hypometabolism treated by ozone therapy.
            (Clavo et al., 2011) Download
BACKGROUND: Radiation-induced brain injury (RBI) and low-perfusion brain syndromes are mediated by ischemia and hypometabolism and have limited treatment options. Ozone therapy as treatment in vascular diseases has been described, but the effects on brain tissue have not been well documented. CASE REPORT: We describe a 75-year-old patient with vascular risk factors and meningioma who was treated with stereotactic radiosurgery. 14 months later the patient presented with progressive clinical impairment despite the use of acetylsalicylic acid and corticosteroids. Clinical and imaging evaluations before/after ozone therapy were done by magnetic resonance imaging (MRI), computed tomography (CT), single photon emission computed tomography (SPECT), and positron emission tomography (PET); performance status assessment was done using Barthel Index and World Health Organization/Eastern Cooperative Oncology Group Scale (WHO/ECOG Scale). Ozone therapy was performed by autohemotransfusion. RESULTS: Basal images showed brain areas with ischemia and hypometabolism compatible with ischemic processes and/or RBI. There were no changes in MRI or CT scan images following ozone therapy. However, improvements in brain perfusion and metabolism were demonstrable with SPECT and PET; they correlated with clinical development and performance status scales. CONCLUSION: This report supports our previous works about the effect of ozone therapy in cerebral blood flow, and it suggests the use of ozone therapy in ischemic and hypometabolic brain syndromes such as stroke or RBI.

Ozone therapy: A clinical review.
            (Elvis and Ekta, 2011) Download
Ozone (O(3)) gas discovered in the mid-nineteenth century is a molecule consisting of three atoms of oxygen in a dynamically unstable structure due to the presence of mesomeric states. Although O(3) has dangerous effects, yet researchers believe it has many therapeutic effects. Ozone therapy has been utilized and heavily studied for more than a century. Its effects are proven, consistent, safe and with minimal and preventable side effects. Medical O(3) is used to disinfect and treat disease. Mechanism of actions is by inactivation of bacteria, viruses, fungi, yeast and protozoa, stimulation of oxygen metabolism, activation of the immune system. Medication forms in a gaseous state are somewhat unusual, and it is for this reason that special application techniques have had to be developed for the safe use of O(3). In local applications as in the treatment of external wounds, its application in the form of a transcutaneous O(3) gas bath has established itself as being the most practical and useful method, for example at low (sub-atmospheric) pressure in a closed system guaranteeing no escape of O(3) into the surrounding air. Ozonized water, whose use is particularly known in dental medicine, is optimally applied as a spray or compress. Diseases treated are infected wounds, circulatory disorders, geriatric conditions, macular degeneration, viral diseases, rheumatism/arthritis, cancer, SARS and AIDS.


Ozone therapy in periodontics.
            (Gupta and Mansi, 2012) Download
Gingival and Periodontal diseases represent a major concern both in dentistry and medicine. The majority of the contributing factors and causes in the etiology of these diseases are reduced or treated with ozone in all its application forms (gas, water, oil). The beneficial biological effects of ozone, its anti-microbial activity, oxidation of bio-molecules precursors and microbial toxins implicated in periodontal diseases and its healing and tissue regeneration properties, make the use of ozone well indicated in all stages of gingival and periodontal diseases. The primary objective of this article is to provide a general review about the clinical applications of ozone in periodontics. The secondary objective is to summarize the available in vitro and in vivo studies in Periodontics in which ozone has been used. This objective would be of importance to future researchers in terms of what has been tried and what the potentials are for the clinical application of ozone in Periodontics.

Ozone therapy effects on biomarkers and lung function in asthma.
            (Hernandez Rosales et al., 2005) Download
BACKGROUND: The relationship and behavior of serum immunoglobulin E (IgE) level, peripheral blood mononuclear cell (PBMC) human leukocyte antigen DR (HLA-DR) expression and erythrocyte glutathione antioxidant pathway in asthma patients treated with systemic ozone therapy have not been studied before. METHODS: Asthma patients were treated about 1 year with three cycles (5 or 6 months each) with three different ozone therapy protocols. Ozone major autohemotherapy (MAHT) was applied at doses of 4 and 8 mg, 15 sessions each cycle; and ozone rectal insufflations (RI) at a dose of 10 mg, 20 sessions each cycle. Serum IgE, HLA-DR expression in PBMC and biomarkers for antioxidant pathway were measured before and at the end of each cycle. Lung function and symptoms test were recorded at the beginning and after the third cycle. RESULTS: IgE and HLA-DR decreased with the three types of treatments, while increments in reduced glutathione, glutathione peroxidase, glutation reductase and glutathione S-transferase were achieved with all treatments. Lung function and symptoms test were markedly improved. However, in all parameters the best response was obtained in the order: MAHT at 8 mg better than MAHT at 4 mg better than RI at 10 mg. Before ozone treatment, glutathione antioxidant parameters were under the normal reference values, suggesting the occurrence of oxidative stress associated with atopic asthma. CONCLUSIONS: This study demonstrates the effectiveness of ozone therapy in reducing IgE and inflammatory mediators along with the induction of antioxidant elements. The study raises the role of systemic ozone therapy in atopic asthma by means of its immunomodulatory and oxidative stress regulation properties.

Ozone therapy as add-on treatment in fibromyalgia management by rectal insufflation: an open-label pilot study.
            (Hidalgo-Tallon et al., 2013) Download
OBJECTIVES: The objectives of this study were to evaluate the effectiveness and tolerability of ozone therapy by rectal insufflation as add-on therapy in fibromyalgia management. DESIGN: Patients with fibromyalgia received 24 sessions of ozone therapy during a 12-week period. At each session, the administered dose of ozone was 8 mg (200 mL of gas, at a concentration of 40 mug/mL). Ozone sessions were given 5 days a week during the first 2 weeks, twice a week from weeks 3-6, and weekly from weeks 7-12. Fibromyalgia Impact Questionnaire (FIQ) was the main outcome measure, and was administered at baseline and at weeks 4, 8, and 12. Secondary outcome measures, administered at baseline and at endpoint, were the Pittsburgh Sleep Quality Index, the Beck Depression Inventory, the State and Trait Anxiety Inventory, and the SF-12, the abbreviated form of the Short Form Health Survey. Emergent adverse reactions to treatment were recorded. RESULTS: FIQ total scores decreased significantly during the study period, with the decrease being observed in the first 4 weeks of the study. Significant improvement was also seen both in depression scores and in the Physical Summary Score of the SF-12. Transient meteorism after ozone therapy sessions was the most frequently reported side-effect. CONCLUSIONS: At the dose and number of sessions used in this study, ozone therapy by rectal insufflation seems to be beneficial for physical symptoms and depression of fibromyalgia.

Ozone therapy as a treatment for low back pain secondary to herniated disc: a systematic review and meta-analysis of randomized controlled trials.
            (Magalhaes et al., 2012) Download
BACKGROUND: Low back pain (LBP) is one of the most common and important health problems affecting the population worldwide and remains mostly unsolved. Ozone therapy has emerged as an additional treatment method. Questions persist concerning its clinical efficacy. OBJECTIVE: The purpose of our study was to evaluate the therapeutic results of percutaneous injection of ozone for low back pain secondary to disc herniation. STUDY DESIGN: A systematic review and meta-analysis of randomized controlled trials. METHODS: A comprehensive literature search was conducted using all electronic databases from 1966 through September 2011. The quality of individual articles was assessed based on the modified Cochrane review criteria for randomized trials and criteria from the Agency for Healthcare Research and Quality. OUTCOME PARAMETERS: The outcome measure was short-term pain relief of at least 6 months or long-term pain relief of more than 6 months. RESULTS: Eight observational studies were included in the systematic review and 4 randomized trials in the meta-analysis. The indicated level of evidence for long-term pain relief was II-3 for ozone therapy applied intradiscally and II-1 for ozone therapy applied paravertebrally. The grading of recommendation was 1C for intradiscal ozone therapy and 1B for paravertebral ozone therapy. LIMITATIONS: The main limitations of this review are the lack of precise diagnosis and the frequent use of mixed therapeutic agents. The meta-analysis included mainly active-control trials. No placebo-controlled trial was found. CONCLUSIONS: Ozone therapy appears to yield positive results and low morbidity rates when applied percutaneously for the treatment of chronic low back pain.

Effects of ozone therapy on haemostatic and oxidative stress index in coronary artery disease.
            (Martinez-Sanchez et al., 2012) Download
Coronary artery disease (CAD) is the most common cause of sudden death, and death of people over 20 years of age. Because ozone therapy can activate the antioxidant system and improve blood circulation and oxygen delivery to tissue, the aim of this study was to investigate the therapeutic efficacy of ozone in patients with CAD, treated with antithrombotic therapy, Aspirin and policosanol. A randomized controlled clinical trial was performed with 53 patients divided into two groups: one (n=27) treated with antithrombotic therapy and other (n=26) treated with antithrombotic therapy plus rectal insufflation of O(3). A parallel group (n=50) age and gender matched was used as reference for the experimental variables. The efficacy of the treatments was evaluated by comparing hemostatic indexes and biochemical markers of oxidative stress in both groups after 20 day of treatment. Ozone treatment significantly (P<0.001) improved prothrombin time when compared to the antithrombotic therapy only group, without modifying bleeding time. Combination antithrombotic therapy+O(3) improved the antioxidant status of patients reducing biomarkers of protein and lipid oxidation, enhancing total antioxidant status and modulating the level of superoxide dismutase and catalase with a 57% and 32% reduction in superoxide dismutase and catalase activities respectively, moving the redox environment to a status of low production of O(2)(*-) with an increase in H(2)O(2) detoxification. No side effects were observed. These results show that medical ozone treatment could be a complementary therapy in the treatment of CAD and its complications.


Mechanisms of Action Involved in Ozone Therapy: Is healing induced via a mild oxidative stress?
            (Sagai and Bocci, 2011) Download
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 (NFkappaB), 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 NFkappaB 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-1alpha (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-1alpha are warranted.


Preliminary results of ozone therapy as a possible treatment for patients with chronic hepatitis C.
            (Zaky et al., 2011b) Download
BACKGROUND: Medical ozone is more bactericidal, fungicidal, and virucidal than any other natural substance. Some studies proved that ozone infused into donated blood samples can kill viruses 100% of the time. Ozone, because of its special biologic properties, has theoretical and practical attributes to make it a potent hepatitis C virus (HCV) inactivator, which suggests an important role in the therapy for hepatitis C. AIM: The study aim is to evaluate the role of ozone therapy in decreasing HCV ribonucleic acid (HCV RNA) load and its effect on the liver enzymes among patients with chronic hepatitis C. METHODS: This study included 52 patients with chronic hepatitis C (positive polymerase chain reaction [PCR] for HCV RNA and raised serum alanine transaminase [ALT] for more than 6 months). All patients were subjected to meticulous history taking and clinical examination. Complete blood count, liver function tests, and abdominal ultrasonography were requested for all patients. The ozone group included 40 patients who received major autohemotherapy, minor autohemotherapy, and rectal ozone insufflation. The other 12 patients (conventional group) received silymarin and/or multivitamins. RESULTS: There were significant improvements of most of the presenting symptoms of the patients in the ozone group in comparison to the conventional group. ALT and aspartate transaminase (AST) levels normalized in 57.5% and 60% in the ozone group, respectively, in comparison to 16.7% and 8% in the conventional group, respectively. Polymerase chain reaction (PCR) for HCV RNA was negative among 25% and 44.4% after 30 and 60 sessions of ozone therapy, respectively, in comparison to 8% among the conventional group. CONCLUSIONS: Ozone therapy significantly improves the clinical symptoms associated with chronic hepatitis C and is associated with normalized ALT and AST levels among a significant number of patients. Ozone therapy is associated with disappearance of HCV RNA from the serum (-ve PCR for HCV RNA) in 25%-45% of patients with chronic hepatitis C.

The effect of rectal ozone on the portal vein oxygenation and pharmacokinetics of propranolol in liver cirrhosis (a preliminary human study).
            (Zaky et al., 2011a) Download
AIM: The aim of this study was to investigate the effect of rectal ozone on portal vein oxygenation and the pharmacokinetic changes of propranolol in patients with liver cirrhosis. METHODS: Fifteen patients with liver cirrhosis were included They were given a fixed oral dose of propranolol 80mg on the morning of day 1 after overnight fasting. Blood samples were collected at fixed time intervals for 24h. Patients were given 12 sessions of rectal ozone of 300ml of 40% ozone/oxygen mixture. On day 14 another oral dose of 80mg propranolol was given and blood samples were collected as on day 1. Plasma concentrations of propranolol were measured by HPLC. Portal vein oxygen tension and saturation were measured before and after rectal ozone. RESULTS: Plasma concentrations of propranolol were reduced after ozone therapy with pronounced decreases in the maximum plasma concentration and the area under the plasma concentration-time curve. The changes were consistent with a decrease in propranolol bioavailability. There was a decrease in the elimination half-life and mean residence time. Portal vein oxygenation significantly increased after rectal ozone. CONCLUSIONS: The changes in the pharmacokinetics of propranolol probably reflect an increase in the rate and extent of its metabolism resulting from improved portal vein oxygenation attributable to the ozone therapy. The present work highlights that ozone can be an alternative medical measure to improve portal vein oxygenation in liver cirrhosis.


References

Bocci, V (1996), ‘Does ozone therapy normalize the cellular redox balance? Implications for therapy of human immunodeficiency virus infection and several other diseases.’, Med Hypotheses, 46 (2), 150-54. PubMedID: 8692040
Bocci, V, et al. (2007), ‘Ozonation of human blood induces a remarkable upregulation of heme oxygenase-1 and heat stress protein-70.’, Mediators Inflamm, 2007 26785. PubMedID: 18274635
Bocci, V, et al. (2009), ‘The ozone paradox: ozone is a strong oxidant as well as a medical drug.’, Med Res Rev, 29 (4), 646-82. PubMedID: 19260079
Bocci, V, I Zanardi, and V Travagli (2011a), ‘Oxygen/ozone as a medical gas mixture. A critical evaluation of the various methods clarifies positive and negative aspects.’, Med Gas Res, 1 (1), 6. PubMedID: 22146387
Bocci, V, et al. (2011b), ‘Diabetes and chronic oxidative stress. A perspective based on the possible usefulness of ozone therapy.’, Diabetes Metab Syndr, 5 (1), 45-49. PubMedID: 22814842
Bocci, VA, I Zanardi, and V Travagli (2011c), ‘Ozone acting on human blood yields a hormetic dose-response relationship.’, J Transl Med, 9 66. PubMedID: 21575276
Clavo, B, et al. (2004a), ‘Ozone Therapy on Cerebral Blood Flow: A Preliminary Report.’, Evid Based Complement Alternat Med, 1 (3), 315-19. PubMedID: 15841265
Clavo, B, et al. (2004b), ‘Ozone Therapy for Tumor Oxygenation: a Pilot Study.’, Evid Based Complement Alternat Med, 1 (1), 93-98. PubMedID: 15257330
Clavo, B, et al. (2011), ‘Brain ischemia and hypometabolism treated by ozone therapy.’, Forsch Komplementmed, 18 (5), 283-87. PubMedID: 22105041
Elvis, AM and JS Ekta (2011), ‘Ozone therapy: A clinical review.’, J Nat Sci Biol Med, 2 (1), 66-70. PubMedID: 22470237
Gupta, G and B Mansi (2012), ‘Ozone therapy in periodontics.’, J Med Life, 5 (1), 59-67. PubMedID: 22574088
Hernandez Rosales, FA, et al. (2005), ‘Ozone therapy effects on biomarkers and lung function in asthma.’, Arch Med Res, 36 (5), 549-54. PubMedID: 16099337
Hidalgo-Tallon, J, et al. (2013), ‘Ozone therapy as add-on treatment in fibromyalgia management by rectal insufflation: an open-label pilot study.’, J Altern Complement Med, 19 (3), 238-42. PubMedID: 23046293
Magalhaes, FN, et al. (2012), ‘Ozone therapy as a treatment for low back pain secondary to herniated disc: a systematic review and meta-analysis of randomized controlled trials.’, Pain Physician, 15 (2), E115-29. PubMedID: 22430658
Martinez-Sanchez, G, et al. (2012), ‘Effects of ozone therapy on haemostatic and oxidative stress index in coronary artery disease.’, Eur J Pharmacol, 691 (1-3), 156-62. PubMedID: 22796450
Sagai, M and V Bocci (2011), ‘Mechanisms of Action Involved in Ozone Therapy: Is healing induced via a mild oxidative stress?’, Med Gas Res, 1 29. PubMedID: 22185664
Zaky, S, EA Fouad, and HI Kotb (2011a), ‘The effect of rectal ozone on the portal vein oxygenation and pharmacokinetics of propranolol in liver cirrhosis (a preliminary human study).’, Br J Clin Pharmacol, 71 (3), 411-15. PubMedID: 21284700
Zaky, S, et al. (2011b), ‘Preliminary results of ozone therapy as a possible treatment for patients with chronic hepatitis C.’, J Altern Complement Med, 17 (3), 259-63. PubMedID: 21417811