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Oxidative Medicine Revisited

Oxidative Medicine Revisited. By Dr. Michael A. Prytula ND and staff. Oxidative Therapies. Include Ozone, UVB, Hydrogen Peroxide, Hyperbaric Oxygen and by mechanism of action…. Ascorbic Acid in high dosages.

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Oxidative Medicine Revisited

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  1. Oxidative Medicine Revisited By Dr. Michael A. Prytula ND and staff

  2. Oxidative Therapies • Include Ozone, UVB, Hydrogen Peroxide, Hyperbaric Oxygen and by mechanism of action…. • Ascorbic Acid in high dosages

  3. Failure of high-dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer. A controlled trial.E.T. Creagan et al., N Med 687 90. High vitamin C Engl J Med. 1979 Sep 27;301(13):687-90. • One hundred and fifty patients with advanced cancer participated in a controlled double-blind study to evaluate the effects of high-dose vitamin C on symptoms and survival. Patients were divided randomly into a group that received vitamin C (10 g per day) and one that received a comparably flavored lactose placebo. • Sixty evaluable patients received vitamin C and 63 received a placebo. Both groups were similar in age, sex, site of primary tumor, performance score, tumor grade and previous chemotherapy. • The two groups showed no appreciable difference in changes in symptoms, performance status, appetite or weight. The median survival for all patients was about seven weeks, and the survival curves essentially overlapped. In this selected group of patients, we were unable to show a therapeutic benefit of high-dose vit C treatment. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=384241&query_hl=10&itool=pubmed_docsum

  4. Tight Control of Ascorbic Acid Plasma Concentrations as a Function of Oral DoseFasting Steady State Concentrations in Plasma in Men (○) and Women (●):

  5. Predicted Plasma Concentrations IV vs Oral

  6. Intravenously administered vitamin C as cancer therapy: three cases Sebastian J. Padayatty, Hugh D. Riordan, Stephen M. Hewitt, Arie Katz, L. John Hoffer, Mark Levine CMAJ • March 28, 2006; 174 (7). http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1405876/pdf/20060328s00017p937.pdf

  7. Abstract Early clinical studies showed that high-dose vitamin C, given by intravenous and oral routes, may improve symptoms and prolong life in patients with terminal cancer. Double-blind placebo-controlled studies of oral vitamin C therapy showed no benefit. Recent evidence shows that oral administration of the maximum tolerated dose of vitamin C (18 g/d) produces peak plasma concentrations of only 220 μmol/L (.220 mM) , whereas intravenous administration of the same dose produces plasma concentrations about 25-fold higher. Larger doses (50–100 g) given intravenously may result in plasma concentrations of about 14 000 μmol/L (14 mM). At concentrations above 1000 μmol/L, vitamin C is toxic to some cancer cells but not to normal cells in vitro. We found 3 well-documented cases of advanced cancers, confirmed by histopathologic review, where patients had unexpectedly long survival times after receiving high-dose intravenous vitamin C therapy. We examined clinical details of each case in accordance with National Cancer Institute (NCI) Best Case Series guidelines. Tumour pathology was verified by pathologists at the NCI who were unaware of diagnosis or treatment. In light of recent clinical pharmacokinetic findings and in vitro evidence of anti-tumour mechanisms, these case reports indicate that the role of high-dose intravenous vitamin C therapy in cancer treatment should be reassessed.

  8. Pharmacologic ascorbic acid concentrations selectively kill cancer cells: Action as a pro-drugto deliver hydrogen peroxide to tissues Qi Chen, Michael Graham Espey, Murali C. Krishna, James B. Mitchell, Christopher P. Corpe, Garry R. Buettner, Emily Shacter, and Mark Levine PNAS September 20, 2005 vol. 102 no. 38 13604-13609 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1224653/pdf/pnas-0506390102.pdf

  9. Abstract Human pharmacokinetics data indicate that i.v. ascorbic acid (ascorbate) in pharmacologic concentrations could have an unanticipated role in cancer treatment. Our goals here were to test whether ascorbate killed cancer cells selectively, and if so, to determine mechanisms, using clinically relevant conditions. Cell death in 10 cancer and 4 normal cell types was measured by using 1-h exposures. Normal cells were unaffected by 20 mMascorbate, whereas 5 cancer lines had EC50 values of <4 mM, a concentration easily achievable i.v.Human lymphoma cells were studied in detail because of their sensitivity to ascorbate (EC50 of 0.5 mM) and suitability for addressing mechanisms. Extracellular but not intracellular ascorbate mediated cell death, which occurred by apoptosis and pyknosisnecrosis. Cell death was independent of metal chelators and absolutely dependent on H2O2 formation. Cell death from H2O2 added to cells was identical to that found when H2O2 was generated by ascorbate treatment. H2O2 generation was dependent on ascorbate concentration, incubation time, and the presence of 0.5–10% serum, and displayed a linear relationship with ascorbate radical formation. Although ascorbate addition to medium generated H2O2, ascorbate addition to blood generated no detectable H2O2 and only trace detectable ascorbate radical. Taken together, these data indicate that ascorbate at concentrations achieved only by i.v. administration may be a pro-drug for formation of H2O2, and that blood can be a delivery system of the pro-drug to tissues. These findings give plausibility to i.v. ascorbic acid in cancer treatment, and have unexpected implications for treatment of infections where H2O2 may be beneficial.

  10. Conditions were chosen tomimic clinical intravenous use • Physiologic (0.1mM) and pharmacologic concentrations (0.3~20mM), adjusted to pH 7 • 1~2 hours exposure • 43 cancer cell lines and 5 types of normal cells • Assays to check survival: MTT, Alamar blue, nuclear staining, colony formation

  11. Pharmacologic ascorbic acid concentrationskill some cancer cells but not normal cells

  12. Concentration dependence of cell death: humanlymphoma (JLP119) vs normal lymphocytes & monocytes

  13. Lymphoma cell death: dependent on extracellular ascorbate extracellular, not intracellular

  14. Mechanism is via H2O2

  15. Inhibition of H2O2 formation in blood:Ascorbate radical formation is minimal

  16. Inhibition of H2O2 formation in blood:Quenching system in blood

  17. Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo Qi Chen, Michael Graham Espey,Andrew Y. Sun, Je-Hyuk Lee, Murali C. Krishna, Emily Shacter, Peter L. Choyke, ChayaPooput, Kenneth L. Kirk,Garry R. Buettner, and Mark Levine PNAS May 22, 2007 vol. 104 no. 21 8749-8754 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1885574/pdf/zpq8749.pdf

  18. Abstract Ascorbate (ascorbic acid, vitamin C), in pharmacologic concentrations easily achieved in humans by i.v. administration, selectively kills some cancer cells but not normal cells. We proposed that pharmacologic ascorbate is a prodrug for preferential steady-state formation of ascorbate radical (Asc) and H2O2 in the extracellular space compared with blood. Here we test this hypothesis in vivo. Rats were administered parenteral (i.v. or i.p.) or oral ascorbate in typical human pharmacologic doses (0.25–0.5 mg per gram of body weight).After i.v. injection, ascorbate baseline concentrations of 50–100 M in blood and extracellular fluid increased to peaks of >8 mM. After i.p. injection, peaks approached 3 mM in both fluids. By gavage, the same doses produced ascorbate concentrations of <150 M in both fluids. In blood, Asc concentrations measured by EPR were undetectable with oral administration and always <50 nM with parenteral administration, even when corresponding ascorbate concentrations were >8 mM. After parenteral dosing, Asc concentrations in extracellular fluid were 4- to 12-fold higher than those in blood, were as high as 250 nM, and were a function of ascorbate concentrations. By using the synthesized probe peroxyxanthone, H2O2 in extracellular fluid was detected only after parenteral administration of ascorbate and when Asc concentrations in extracellular fluid exceeded 100 nM. The data show that pharmacologic ascorbate is a prodrug for preferential steady-state formation of Asc and H2O2 in the extracellular space but not blood. These data provide a foundation for pursuing pharmacologic ascorbate as a prooxidant therapeutic agent in cancer and infections.

  19. Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice Qi Chen, Michael Graham Espey, Andrew Y. Sun, ChayaPooput, Kenneth L. Kirk, Murali C. Krishna, Deena BenedaKhosh, Jeanne Drisko, and Mark Levine PNAS August 12, 2008 vol. 105 no. 32 11105–11109 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2516281/pdf/zpq11105.pdf

  20. Abstract Ascorbic acid is an essential nutrient commonly regarded as an antioxidant. In this study, we showed that ascorbate at pharmacologic concentrations was a prooxidant, generating hydrogenperoxide- dependent cytotoxicity toward a variety of cancer cells in vitro without adversely affecting normal cells. To test this action in vivo, normal oral tight control was bypassed by parenteralascorbate administration. Real-time microdialysis sampling in mice bearing glioblastomaxenografts showed that a single pharmacologic dose of ascorbate produced sustained ascorbate radical and hydrogen peroxide formation selectively within interstitial fluids of tumors but not in blood. Moreover, a regimen of daily pharmacologic ascorbate treatment significantly decreased growth rates of ovarian (P < 0.005), pancreatic (P < 0.05), and glioblastoma (P < 0.001) tumors established in mice. Similar pharmacologic concentrations were readily achieved in humans given ascorbate intravenously. These data suggest that ascorbate as a prodrug may have benefits in cancers with poor prognosis and limited therapeutic options.

  21. Ascorbic acid as a function of time in blood, extracellular fluid, and tumors with 4 g/kg i.p. ascorbate

  22. Vit C: Prooxidant! • IV or IP ascorbateadministration creates pro-oxidant ascorbate radical and H2O2 in extracellular fluids but not in blood, consistent with their roles as tumor cytotoxic effectors. • IV or IP administration achieves pharmacologic concentrations of ascorbic acid, generating ascorbateradical and H2O2 in tissues, with anti cancer effects, and may have effects on diseases that H2O2 or ROS have therapeutic roles, such as infections.

  23. Book: Hope, Medicine & Healingby Francisco Contreras, MD & Daniel E. Kennedy, MC

  24. …It is clear that, in terms of survival, Oasis of Hope patients are doingbetter than those receiving the average standard of care in the U.S. Inparticular, survival in lung cancer is strikingly better… our results withstage 4 breast cancer patients who came to Oasis soon after diagnosisare quite good – a doubling of two-year survival relative to conventional therapy.---excerpt from the book

  25. Hazardous Waste and Hazardous Materials ChemicalOxidation Technologies: Ultraviolet Light/HydrogenPeroxide, Fenton's Reagent, and Titanium Dioxide-Assisted Photocatalysis RAJAGOPALAN VENKATADRI, ROBERT W. PETERS. Hazardous Waste and Hazardous Materials. Spring1993, 10(2): 107-149.doi:10.1089/hwm. 1993.10.107. Published in Volume: 10 Issue 2: April10, 2009 Mary Ann Liebert, Inc. Publishers http://www.liebertonline.com/doi/abs/10.1089/hwm.1993.10.107

  26. Abstract The application status and potential of three chemical oxidation treatment methods which generate powerful oxidants (hydroxyl radicals): ultraviolet light (UV)/hydrogen peroxide (H2O2) process, Fenton's reagent treatment, and titanium dioxide (TiO2)-assisted photocatalytic degradation, are described and discussed. These oxidation methods are known to effectively degrade and, in several cases, mineralize contaminants ranging from inorganic compounds (such as cyanides) to chlorinated aliphatic compounds and complex aromatic compounds in reaction times on the order of a few minutes to a few hours. Of the three oxidation systems discussed, the technology for the UV/H2O2 process is the most advanced, with numerous successful full-scale treatment units already in existence. Applications of both the Fenton's reagent and TiO2-assisted photodegradation processes are currently being developed, with the concepts proven in numerous laboratory-scale studies for a wide range of contaminants. However, both of these processes have only been studied at the pilot/field scale to a limited extent. The application of Fenton's reagent as a pretreatment step prior to biological treatment for industrial wastes and contaminated soils appears promising. Improved system configuration and quantum efficiency of photoreactors are likely to improve the economics of TiO2-assisted photodegradation for groundwater treatment, especially with the use of solar illumination.

  27. Degradation of Endocrine Disrupting Chemicals by Ozone/AOPs BO NING; GRAHAM Nigel; YANPING ZHANG; NAKONECHNY Maureen; MOHAMED GAMAL EL-DIN Published in: Ozone: Science & Engineering, Volume 29, Issue 3 May 2007 , pages 153 – 176 http://www.informaworld.com/smpp/content~db=all~content=a779407475?words=ozone|cancer&hash=3509892760

  28. Abstract The presence of endocrine-disrupting compounds (EDCs) in the aqueous environment is of increasing concern due to their adverse impact on aquatic life, and potential risk to human health. Among the EDCs of concern are steroidal estrogenic hormones such as estrone (E1), 17β-estradiol (E2), estriol (E3), and 17 -ethinylestradiol (EE2), which have a high environmental prevalence and strong estrogenic activity. In addition, the extensive use of alkylphenolethoxylates (APnEOs), bisphenol A (BPA) and phthalate compounds have resulted in an environmental presence at significant concentrations, although they appear to have a lower estrogenic activity than the steroidal hormones. As water and wastewaters are some of the primary routes of exposure to EDCs, it is important to determine at what levels EDCs are found in these media and how these levels may be reduced. Hence, it is necessary to understand the fate of EDCs in conventional water and wastewater treatment plants, as well as the efficacy of more specialized treatment methods, such as adsorption and oxidation. This paper is a summary of the latest information on the degradation of prominent EDCs by ozone and ozone-based advanced oxidation processes (AOPs). From this review, it is clear that ozone and AOPs are effective in degrading these EDCs, with the possible exception of phthalates, which are relatively stable to ozone oxidation. Knowledge of the formation of reaction products from the treatment by ozone and AOPs is relatively poor at present, particularly for the non-steroid compounds.

  29. Ozone Therapy in Cancer Treatment: State of the Art Silvia Menndeza; Janet Ceperob; Luis Borregoc Published in: Ozone: Science & Engineering, Volume 30, Issue 6 November 2008 , pages 398 - 404 http://www.informaworld.com/smpp/content~db=all~content=a905990487?words=ozone|cancer&hash=3509892760

  30. Abstract ErhlichAscitic Tumor and Sarcoma 37 were implanted in mice and afterward the animals were treated with ozone (rectally). A significant decrease in the number of metastasis was obtained. In another study, ozone was applied intraperitoneally, before Lewis' lung carcinoma inoculation. A delayed effect in the tumor development kinetics and in the increase rate of tumor volume in the ozone groups was observed. With regard to the clinical trial, patients with prostatic cancer were treated with cobalt-60 therapy and ozone (rectally), decreasing the presence of side effects (due to radiation treatment) and the prostatic specific antigen figures. However, further investigations are necessary to be performed, in order to be considered the ozone therapy as complementary therapy for cancer.

  31. Alist of clinically useful medicinaloxidants: • inorganic oxidants: hyperbaric oxygen (O2), singlet oxygen (O2), ozone (O3), hydrogen peroxide (H2O2), magnesium peroxide (MgO2), zinc peroxide (ZnO2), chlorine dioxide (ClO2), chlorite (ClO2-), nitrate ( NO3-), permanganate ( MnO4-), iodine ( I2) • organic oxidants: organic ozonides (RO3R'), organic peroxides (ROOR'), quinones(Q), alphaketoaldehydes RCOCHO), imidazoles, methyleneblue • sulfur compounds:disulfides (RSSR'), sulfoxides (RSOR'), disulfide monoxides (RSSOR') • utravioletlight • Ascorbates (in high doses)

  32. UV - IM Technique • Withdraw 5cc blood into syringe. Attach to special UVI cuvette. • Pass blood into cuvette, but do not remove syringe. • Insert cuvette, syringe attached, into receptacle in machine. • Turn on timed cycle. • When cycle complete, withdraw blood into syringe , remove from cuvette. • Attach needle and inject IM

  33. Antibodies Generate Ozone!!Science News, December 2002 • Antibodies have the capacity, on their own, to generate ozone. Investigators found oxidation reactions that could only be attributed to the presence of ozone. • They believed the raw material source was singlet oxygen generated by activated neutrophils, which provides the energy needed for the antibodies to manufacture ozone • Hence, ozone is a natural substance produced by the body.

  34. Investigating antibody-catalyzed ozone generation by human neutrophils Bernard M. Babior,, Cindy Takeuchi§, Julie Ruedi, Abel Gutierrez, and Paul Wentworth Jr Departments of Molecular and Experimental Medicine, Immunology, Chemistry, and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 Contributed by Bernard M. Babior, January 14, 2003 PNAS | March 18, 2003 | vol. 100 | no. 6 | 3031-3034 From the Cover Chemistry / Biochemistry

  35. Abstract • Recent studies have suggested that antibodies can catalyze the generation of previously unknown oxidants including dihydrogen trioxide (H2O3) and ozone (O3) from singlet oxygen (1O2)and water. Given that neutrophils have the potential both to produce 1O2 and to bind antibodies, we 2 considered that these cells could be a biological source of O3. • We report here further analytical evidence that antibody-coated neutrophils, after activation, produce an oxidant with the chemical signature of O3. This process is independent of surface antibody concentration down to 50% of the resting concentration, suggesting that surface IgG is highly efficient at intercepting the neutrophil-generated 1O2 • Vinylbenzoic acid, an orthogonal probe for ozone detection, is oxidized by activated neutrophils to 4-carboxybenzaldehyde in a manner analogous to that obtained for its oxidation by ozone in solution. This discovery of the production of such a powerful oxidant in a biological context raises questions about not only the capacity of O3 to kill invading microorganisms but also its role in amplification of the inflammatory response by signaling and gene activation

  36. The effects of colorectally insufflated oxygen-ozone on red blood cell rheology in rabbits. A. SedaArtis, S. Aydogan & M. GokhanSahin. ClinHemorheolMicrocirc. 2010;45(2-4):329-36. • Erythrocyte deformability, aggregation and osmotic fragility were determined from blood samples at the end of each treatment period. • The study showed an improvement in deformability, a decrease in aggregation and an increase in fragility following a 15 day ozone treatment. • With longer ozone application the changes in aggregation and fragility returned back to control levels, however its effect on deformability sustained. Therefore, more than two weeks ozone insufflation may induce adaptation to changes induced by ozone suggesting its systemic effects.

  37. Effect of ozone/oxygen mixture on systemic oxidative stress and organic damage. D. Guanche, Z. Zamora, F. Hernádez, K. Mena, Y. Alonso et al. ToxicolMech Methods. 2010 Jan;20(1):25-30. • Ozone doses administered to rabbits did not cause adverse effects and mortality did not show significant changes relative to tissue damages and they increased enzymes activities belonging to the first line antioxidant defences. The results demonstrate that ozone/oxygen mixture administered by rectal insufflations is innocuous and it is able to increase the antioxidant defense of the organism.

  38. Oxygen-ozone therapy in medicine: an update V. Bocci, N. Di Paolo. Blood Purif. 2009;28(4):373-6. Epub 2009 Sep 10 • Ozone therapy is particularly useful in cardiovascular disorders and tissue ischemia. In chronic viral infections, it is unable to eliminate the viremia but it may display supportive help by stimulating the immune system. Recently, its use has been successfully extended to the herniated disk pathology and therapy of primary caries in children.

  39. Experience with the use of ozone for the treatment of chronic viral hepatitis V.A. Neronov. Vopr Kurortol Fizioter Lech Fiz Kult. 2009 Nov-Dec;(6):14-7. • Patients treated with the use of ozone exhibited better biochemical, virological, and functional characteristics compared with their counterparts managed by standard methods. The results of the study suggest a higher efficiency of combined therapy and reduced risk of development of cholelithiasis.

  40. Oxidative stress level in patients with rosacea and a rationale for the therapeutic use of an ozone-oxygen mixture O.A. Bitkina, T.V. Kopytova, K.N. Kontorshchikova, A.P. Bavrina. Klin Lab Diagn. 2010 Apr;(4):13-6. • Eighty patients with different clinical types of rosacea were examined; the parameters of primary and intermediate products of lipid peroxidation, superoxide dismutase, plasma total antioxidative activity, and protein oxidative modification were studied. Based on the findings, oxidative therapy options for rosacea, treatment with an ozone-oxygen mixture in particular, are proposed.

  41. Application of ozone therapy in complex treatment of patients with acute necrotizing pancreatitis V.M. Kopchak, I.V. Khomiak, A.V. Duvalko, A.A. Stasenko, V.A. Dieiev. KlinKhir. 2008 Oct;(10):28-31. • Examination and treatment of 32 patients was done, in whom an acute necrotic pancreatitis was diagnosed. In 16 patients (the main group) ozonotherapy, according to scheme, elaborated in the clinic, was added to conventional treatment. The ozonotherapy application had permitted to reduce the rate of performance of "open" operative interventions. The cellular, humoral and local immunity improvement and biochemical indices normalization were noted. The stationary treatment duration was 21.4 days at average in the main group and 34.5 -- in a control one. The relaparotomy performance rate in the main group was lesser than in a control one.

  42. Efficacy of hyperbaric oxygen therapy and medical ozone therapy in experimental acute necrotizing pancreatitis B. Uysal, M. Yasar, N. Ersoz, O. Coskun, A. Kilic et al. Pancreas. 2010 Jan;39(1):9-15. • Forty Sprague-Dawley rats were divided into sham-operated, acute necrotizing pancreatitis (ANP), ANP + hyperbaric oxygen (HBO), and ANP + ozone therapy (OT) groups. • Serum amylase/lipase and neopterin levels and tissue oxidative stress parameters were similar to sham's values in both the ANP + HBO and the ANP + OT groups. Histopathologic injury scores were significantly lower in the treatments groups than in the ANP group. • Hyperbaric oxygen and OT reduce the severity and the mortality in the experimental rat model of ANP, and a greater benefit was received for OT comparing with HBO.

  43. Treatment of patients with acute and chronic suppurative middle ear diseases using ozone preparations E.V. Sin’kov. VestnOtorinolaringol. 2009;(3):34-5. • Methods of clinical application of gaseous ozone and ozonated solutions for 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 suppurativeotitis media.

  44. May oxygen-ozone therapy improves cardiovascular disorders? V. Bocci, V. Travagli, I. Zanardi. CardiovascHematolDisord Drug Targets. 2009 Jun;9(2):78-85. • In an aging population vascular disorders well exemplified by the chronic limb ischemia, chronic heart failure, cerebral ischemia and age-related macular degeneration represent a serious medical and socio-economical problem. All of these diseases are characterized by ischemia, chronic inflammation and tissue degeneration. Here it is proposed to associate the approach of ozonatedautohemotherapy as a modifier of the biological response capable to block the pathological progress

  45. Ozone therapy in lumbar sciatic painM.D'Erme et al. Radiol Med. 1998 Jan-Feb;95(1-2):21-4. • MATERIAL AND METHODS: September, 1995, to April, 1997, we treated more than 1000 patients with intradiscal ozone infiltration. We prospectively analyzed the first 50 patients, with 6 months' follow-up at least; all of them were preliminarily submitted to clinical examination, electromyography, CT and MRI. After local anesthesia, we injected the disk, with 18-20 G needles and under CT or fluoroscopic guidance, with 12 ml of a mixture of oxygen and ozone at a concentration of 20-30 micrograms/ml. The treatment was repeated two or three more times at intervals of 3, 15 or, when necessary, 30 days. After each treatment, CT follow-ups were carried out and the final follow-up was made 3 months later.

  46. RESULTS: We divided our results into clinical and instrumental. As for clinical response, we had 68% positive results (40% excellent, 28% good) and 32% negative results (10% of patients underwent surgery and 22 are under medical and physical treatment). As for CT response, we had 82% positive results (36% excellent, 46% good), while no major changes between pre- and post-treatment CT findings in the remaining 18% of cases. • CONCLUSIONS: Ozone therapy, thanks to its ease of execution and noninvasiveness, permits the successful outpatient treatment of lumbar sciatic pain. Moreover, the lack of major complications and the good results obtained compared to other methods, such as chemonucleolysis, percutaneous automated discectomy, microsurgery and conventional surgery, suggest that ozone therapy can be considered the treatment of choice for lumbar sciatic pain and a valid alternative to surgery in many cases.

  47. Minimally invasive oxygen-ozone therapy for lumbar disk herniation.C.F. Andreula et al., AJNR Am J Neuroradiol. 2003 May;24(5):996-1000 • METHODS: Six hundred patients were treated with a single session of oxygen-ozone therapy. All presented with clinical signs of lumbar disk nerve root compression, with CT and/or MR evidence of contained disk herniation. Three hundred patients (group A) received an intradiscal (4 mL) and periganglionic (8 mL) injection of an oxygen-ozone mixture at an ozone concentration of 27 micro g/mL. The other 300 patients (group B) received, in addition, a periganglionic injection of corticosteroid and anesthetic. Therapeutic outcome was assessed 6 months after treatment by using a modified MacNab method. Results were evaluated by two observers blinded to patient distribution within the two groups.

  48. RESULTS: A satisfactory therapeutic outcome was obtained in both groups. In group A, treatment was a success (excellent or good outcome) in 70.3% and deemed a failure (poor outcome or recourse to surgery) in the remaining 29.7%. In group B, treatment was a success in 78.3% and deemed a failure in the remaining 21.7%. The difference in outcome between the two groups was statistically significant (P <.05). • CONCLUSION: Combined intradiscal and periganglionic injection of medical ozone and periganglionic injection of steroids has a cumulative effect that enhances the overall outcome of treatment for pain caused by disk herniation. Oxygen-ozone therapy is a useful treatment for lumbar disk herniation that has failed to respond to conservative management.

  49. Treatment of herniated lumbar disc by intradiscal and intraforaminal oxygen-ozone (O2-O3) injection M. Muto, C. Andreula, M. Leonardi. J Neuroradiol. 2004 Jun;31(3):183-9 • MATERIAL: We report our experience between May 1996 and May 2003 with 2200 patients affected by low back pain or sciatica due to herniated disk treated by intradiscal and intraforaminal oxygen-ozone injection. The patients received medical and physical therapy before treatment for at least 2 months; the patients with conus-cauda syndrome and hyperalgesic sciatica were excluded. We never performed discography before the treatment that was performed under CT guidance or fluoroscopy. CT provided monitoring of gas distribution in the disk and epidural space. • RESULTS: No side effects were recorded at short and long-term follow-up. Clinical results were evaluated with the modified McNab method showing an 80% success rate and 20% failure rate in 1750 patients followed up to 6 monthswhile the success rate dropped down at 75% and failure increased at 25% in 1400 followed up to 18 months. CT showed reduction in the size of the herniated disk in only 63% of the followed patients (420 patients). The failure has been mostly related to: calcified herniated disk; spinal canal stenosis; recurrent herniated disk with epidural fibrosis; small descending herniated disk at the level of the lateral recess.

  50. Ozone nucleolysis for management of pain and disability in prolapsed lumber intervertebral disc. A prospective cohort study. G. Das, S. Ray, S. Ishwarari, M. Roy, P. Ghosh. IntervNeuroradiol. 2009 Sep;15(3):330-4. Epub 2009 Nov 4. • Pain intensity was significantly reduced following treatment (Visual Analog Score baseline 7.58-/+0.86, after three weeks 2.75-/+1.42 and after two years 2.64-/+2.14). • Oswestry disability index showed a remarkable improvement in the functional status of the patients (p<0.05). • Oxygen-ozone treatment is highly effective in relieving low back pain due to lumber disc herniation.

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