Ozone Therapy in Refractory Pelvic Pain Syndromes Secondary to Cancer Treatment: A New Approach Warranting Exploration.

Background: Chronic pain secondary to treatment in cancer survivors without tumor evidence is not unusual. Its management often requires specific approaches that are different from those applied for cancer patients with advanced disease and short life expectancy. Some studies have described clinical benefit with ozone therapy (O3T) in the management of pain and side effects secondary to cancer treatment. Objective: We present our preliminary experience with O3T in the management of refractory pelvic pain syndromes secondary to cancer treatment. Design: Case series. Subjects and Methods: Six cancer patients (without tumor evidence) who had been treated previously with radiotherapy, chemotherapy, or endoscopic procedures and were suffering persistent or severe pelvic pain (median 14 months) received O3T using ozone-oxygen gas mixture insufflation as a complementary therapy in addition to their scheduled conventional treatment. Results: All cases, except one, showed clinically relevant pain improvement. Visual analog scale score with the standard treatment was 7.8 ± 2.1 before O3T, 4.3 ± 3.4 (p = 0.049) after one month, 3.3 ± 3.7 (p = 0.024) after two months, and 2.8 ± 3.8 (p = 0.020) after three months of O3T. The median value of "pain symptom" according to the U.S. National Cancer Institute Common Terminology Criteria for Adverse Events v. 5.0 showed a decrease from 3 (range: 2-3) to 1 (range: 0-3) (p = 0.046). Conclusions: Following unsuccessful conventional treatments, O3T provided significant benefit in our patients with refractory pelvic pain secondary to cancer treatment. These results merit further evaluation in blinded, randomized clinical trials.

Reduction of non-enzymatic antioxidants in plasma during ECMO-treatment in ARDS by influence A H1N1.

PURPOSE: In critically ill patient it is observed a severe oxidative stress, not only due to the acute pathology but also for some therapeutic treatments. The aim of the present study was to analyze the variations of non-enzymatic antioxidants in plasma during veno-venous ECMO-treatment in a homogeneous population of critical patients with ARDS. MATERIALS AND METHODS: We carried out a retrospective study enrolling all patients with ARDS by influence A H1N1 treated with veno-venous ECMO. In all patients included, we have recorded clinical and laboratory parameters considered indicators of oxidative stress during the first week of treatment. RESULTS: With regard to non-enzymatic antioxidants evaluated, we observed that both albumin and uric acid decreased significantly, at all observation times, after ECMO-treatment [(25.88±4.51, 18.05±4.27, 16.32±4.57, 19.07±5.10, p<0.05)(g/l), (5.46±1.43, 2.30±1.15, 2.90±2.09, 2.07±1.03, p<0.05)(mg/dl), respectively]. At the same time the amount of insulin administered daily was increased with statistical significance (p=0.03). CONCLUSIONS: The veno-venous ECMO-treatment causes a significant reduction of some of the major non-enzymatic antioxidants and a possible increase in insulin resistance in patients with ARDS by influence A H1N1.

Validity of Oxygen-Ozone Therapy as Integrated Medication Form in Chronic Inflammatory Diseases.

The state-of-the-art of oxygen-ozone therapy is now clarified and all the mechanisms of action of medical ozone are within classical biochemistry and molecular biology. The outcomes of standard treatments in peripheral arterial occlusive disease (PAOD) and dry-form of age-related macular degeneration (AMD) have been compared with the documented therapeutic results achieved with ozonated autohemotherapy (O-AHT). On the other hand, the clinical data of O-AHT on stroke remain indicative. As the cost of O-AHT is almost irrelevant, its application in all public hospitals, especially those of poor Countries, would allow two advantages: the first is for the patient, who will improve her/his conditions, and the second is for Health Authorities burdened with increasing costs. The aim of this paper is to report to clinical scientists that O-AHT is a scientific-based therapeutic approach without side effects. The integration of O-AHT with effective approved drugs is likely to yield the best clinical results in several chronic inflammatory diseases.

The usefulness of ozone treatment in spinal pain.

OBJECTIVE: The aim of this review is to elucidate the biochemical, molecular, immunological, and pharmaceutical mechanisms of action of ozone dissolved in biological fluids. Studies performed during the last two decades allow the drawing of a comprehensive framework for understanding and recommending the integration of ozone therapy for spinal pain. METHODS: An in-depth screening of primary sources of information online - via SciFinder Scholar, Google Scholar, and Scopus databases as well as Embase, PubMed, and the Cochrane Database of Systemic Reviews - was performed. In this review, the most significant papers of the last 25 years are presented and their proposals critically evaluated, regardless of the bibliometric impact of the journals. RESULTS: The efficacy of standard treatments combined with the unique capacity of ozone therapy to reactivate the innate antioxidant system is the key to correcting the oxidative stress typical of chronic inflammatory diseases. Pain pathways and control systems of algesic signals after ozone administration are described. CONCLUSION: This paper finds favors the full insertion of ozone therapy into pharmaceutical sciences, rather than as either an alternative or an esoteric approach.

Visual improvement following ozonetherapy in dry age related macular degeneration; a review.

The dry form of ARMD is becoming a serious problem because of the rise in the number of old individuals. No effective therapy is available in dry ARMD except for the illusory oral administration of antioxidant vitamins. Despite scepticism in the medical community, the therapeutic effect of ozonetherapy had been evaluated since 1996. This evaluation has been based on specific biochemical, molecular and pharmacological reactions. Nevertheless a number of visual scientists continue to ignore ozonetherapy conservatively and prescribe only antioxidant vitamins. Two small clinical studies involving 217 patients have been performed at the University of Siena showing that ozonetherapy can stop the progression of the disease while improving the visual acuity and the well-being of the patient. Moreover, it seems that ozonetherapy is a safe procedure and tends to have an excellent compliance.

Reliable and effective oxygen-ozone therapy at a crossroads with ozonated saline infusion and ozone rectal insufflation.

OBJECTIVES: This review aims to highlight the advantages and safety of oxygen-ozone therapy (OOT) and to suggest ways to enhance its acceptance. KEY FINDINGS: The treatment of a herniated disk by injecting a gaseous oxygen-ozone mixture inside the nucleus pulposus is a great clinical success. However, the use of OOT lags for a number of reasons, including lack of standardization, the need for numerous treatments, lack of knowledge and even denial. Anecdotally, several million treatments by OOT have been performed worldwide indicating its usefulness, mainly in peripheral arterial diseases and age-related macular degeneration. The scepticism that accompanies the systemic use of ozone can only be overcome by demonstrating the validity of OOT in controlled and randomized clinical trials. Cheaper and quicker methods, such as ozonating physiological saline with successive infusion as well as ozone rectal insufflations, are becoming popular, however, such alternative procedures are erratic, unstable and liable to be toxic, with deleterious consequences, and are likely to discredit the beneficial use of ozone. SUMMARY: The approval of ozone in terms of both therapeutic efficacy and safety will depend on the results achieved by authoritative clinical trials.

Effects of major ozonated autohemotherapy in the treatment of dry age related macular degeneration: a randomized controlled clinical study.

AIM: To evaluate the effect of systemic ozonated major autohaemotherapy (O(3)-AHT) in patients affected by dry age related macular degeneration (AMD). METHODS: This study was a randomized, controlled clinical study. One hundred and forty patients with the diagnosis of AMD in both eyes, with the study eye presenting dry AMD and soft drusen, were randomly assigned in a 1:1 ratio to either receive 27 major ozonated autohemotherapy treatments during 12-month period, or a standardized multi-vitamin therapy. Primary outcome was the change in best corrected visual acuity (mean logMar change) between the baseline and 6 and 12 months, end point of the study. In addition, to investigate the safety of prolonged ozonated autohaemotherapy, we measured the routine haematochemical parameters and biochemical oxidative stress values at baseline and after 12 months treatment time. RESULTS: The mean baseline best corrected visual acuity in study eyes was 0.36 in the treatment group and 0.38 in the control group (difference not statistically significant). At the primary endpoint, 6 months post-baseline, the mean logMAR change in the treated group improved by 0.1 and the values of the control group at the same time impaired by 0.2 respect to the baseline. Four percent and twenty-five percent of eyes in the group treated with O(3)-AHT gained 1 or more lines after 6 and 12 months respectively compared to 0% in the eyes which received no treatment (P<0.05 at 12 months). None of the treated patients experienced a loss in visual acuity in their study eye at 6 and 12 months, compared to 16% and 40 % of patients in the control group who lost 2 lines or more at 6 months and 12 months respectively (P<0.05 treated vs control group)). Major ozonated autohemotherapy was shown to be safe and well- tolerated by the patients. Moreover, the haematochemical parameters showed a decrease in the Reactive Oxygen Metabolites (300±10.1 UCARR at 12 months compared to a baseline value of 380±10.4 UCARR, P<0.05) and an increase in Biological Antioxidant Potential plasma values (2100±34.8 micromoles/ C vitamin after 12 months compared to the baseline value of 1610±36.2, P<0.05) in the treated patients when compared to the control group. This data suggests that major ozonated autohaemotherapy may exert a role in reducing oxidative stress by endogenously stimulating the production of antioxidant molecules. CONCLUSION: The results of this study suggests that major ozonated autohaemotherapy could be a safe and effective therapeutic option for high-risk patients with dry AMD, and that a series of such treatments could improve the natural course of AMD.

Mechanism of action of oxygen ozone therapy in the treatment of disc herniation and low back pain.

In the low back syndrome the pain has a multifactorial origin and ozone can surprisingly display a number of beneficial effects ranging from the inhibition of inflammation, correction of ischemia and venous stasis, and finally inducing a reflex therapy effect by stimulating anti-nociceptor analgesic mechanisms. The intradiscal and intramuscular injection of oxygen-ozone is a successful approach comparable to other minimally invasive procedures, but the elucidation of the mechanisms of action remains elusive. This communication shortly reports the mechanisms of action of oxygen ozone therapy at the level of intervertebral disc and paravertebral muscles.

Interleukin 6 activity associated with a cardiac lymphoma.

Primary cardiac B-cell lymphoma is an extremely rare heart tumor that may be difficult to diagnose because of nonspecific clinical manifestations. Cardiac myxomas and mediastinal lymphomas show increased levels of serum cytokines, which correlate with symptoms and tumor size. We present a case of an intracardiac large B-cell lymphoma in a 75-year-old woman who had high serum levels of interleukin 6 that decreased after tumor excision. These data suggest a possible correlation between cardiac B lymphoma symptoms and interleukin 6 overproduction.

The ozone paradox: ozone is a strong oxidant as well as a medical drug.

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.

Noninvasive evaluation of skeletal muscle oxidative metabolism after heart transplant.

PURPOSE: The main aim of the present study was to investigate skeletal muscle oxidative metabolism in heart transplant recipients (HTR) by noninvasive tools. METHODS: Twenty male HTR (age 50.4 +/- 2.6 yr; mean +/- SE) and 17 healthy untrained age-matched controls (CTRL) performed an incremental exercise (IE) and a series of constant-load (CLE) moderate-intensity exercise tests on a cycloergometer. The following variables were determined: heart rate (HR); breath-by-breath pulmonary O2 uptake (VO2); and skeletal muscle (vastus lateralis) oxygenation indices by continuous-wave near-infrared spectroscopy. Changes in concentration of deoxygenated hemoglobin (Hb) and myoglobin (Mb) (Delta[deoxy(Hb + Mb)]), expressed as a fraction of values obtained during a transient limb ischemia, were taken as an index of skeletal muscle O2 extraction. "Peak" values were determined at exhaustion during IE. Kinetics of adjustment of variables were determined during CLE. RESULTS: VO2peak, HRpeak, and Delta[deoxy(Hb + Mb)] peak were significantly lower in HTR than in CTRL (17.1 +/- 0.7 vs 34.0 +/- 1.9 mL.kg(-1).min(-1), 133.8 +/- 3.8 vs 173.0 +/- 4.8 bpm, and 0.42 +/- 0.03 vs 0.58 +/- 0.04, respectively). In HTR, Delta[deoxy(Hb + Mb)] increase at submaximal workloads was steeper than in CTRL, suggesting an impaired O2 delivery to skeletal muscles, whereas the lower Delta[deoxy(Hb + Mb)] peak values suggest an impaired capacity of O2 extraction at peak exercise. VO2 and HR kinetics during CLE were significantly slower in HTR than in CTRL, whereas, unexpectedly, no significant differences were found for Delta[deoxy(Hb+Mb)] kinetics (mean response time: 21.3 +/- 1.1 vs 20.2 +/- 1.2 s). CONCLUSION: The findings confirm the presence of both "central" (cardiovascular) and "peripheral" (at the skeletal muscle level) impairments to oxidative metabolism in HTR. The noninvasiveness of the measurements will allow for serial evaluation of the patients, in the presence and/or absence of rehabilitation programs.

Serial assessment of peak VO2 and VO2 kinetics early after heart transplantation.

PURPOSE: Serial evaluation of aerobic metabolism and exercise tolerance early after heart transplantation (HT). METHODS: Fifteen heart transplant recipients (HTR), aged 52.0 +/- 9.9 yr (mean +/- SD), not undergoing structured rehabilitation programs, were tested two to four times during the first 2 yr post-HT. As a reference, a group of 11 healthy untrained controls (C) was utilized. Peak heart rate (peak HR), peak O2 uptake (peak VO2), and ventilatory threshold (VT) were determined during incremental bicycle exercise to voluntary exhaustion. VO2 kinetics were evaluated during constant-load exercise below VT, with determination of the duration of the "cardiodynamic" component (TDp) and of the time constant of the "primary" component (taup). RESULTS: Peak VO2 (L.min-1) was positively related to months post-HT (y=1.17 + 0.02x, P=0.003), and it increased by approximately 30% during the investigated period, although values in HTR were lower than in C (2.19 +/- 0.24). Peak HR was lower in HTR (136 +/- 15 beats.min-1) than in C (168 +/- 5), and it was not related to time post-HT. TDp was longer in HTR (31.4 +/- 6.3 s) than in C (23.2 +/- 6.1), and it was not related to time post-HT. A subgroup of HTR with markedly longer taup during the first months post-HT showed a significant decrease of this parameter as a function of time post-HT. CONCLUSIONS: Aerobic metabolism is impaired in HTR. Both central (cardiovascular) and peripheral (skeletal muscle) factors contribute to the reduced exercise tolerance. HTR showed, during the first 2 yr post-HT, a significant increase in peak VO2 and (in the patients with the slowest VO2 kinetics during the first months after HT) a significant improvement of the VO2 kinetics. The main gains seem to occur at the peripheral level.

Myocardial and lung injury after cardiopulmonary bypass: role of interleukin (IL)-10.

BACKGROUND: Proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-8 play a key role in the inflammatory cascade after cardiopulmonary bypass (CPB) and may induce cardiac and lung dysfunction. Antiinflammatory cytokines such as IL-10 may also significantly limit these complications. Corticosteroid administration before CPB increases blood IL-10 levels and prevents proinflammatory cytokine release. This study examined the association of increased release of IL-10, stimulated by steroid pretreatment, with reduced myocardial and lung injury after CPB. METHODS: Twenty patients undergoing coronary artery bypass grafting (CABG) received either preoperative steroid (n = 10, protocol group) or no steroid (n = 10, control group). Perioperative care was standardized, and all caregivers were blinded to treatment group. Seven intervals of blood samples were obtained and assayed for TNF-alpha, IL-6, IL-8, and IL-10. Various hemodynamic and pulmonary measurements were obtained perioperatively. Levels of MB isoenzyme creatine kinase (CK-MB) were also measured. RESULTS: In the protocol group, proinflammatory cytokines were significantly reduced while IL-10 levels were much higher after CPB. The protocol group had a lower alveolar-arterial oxygen gradient and higher ratio of arterial oxygen pressure to fraction of inspired oxygen after CPB. Creatine kinase (CK) and CK-MB were reduced in the patients treated with steroid. Correlations were found between plasma cytokines levels and cardiac index, and CK-MB. CONCLUSIONS: This study confirms that corticosteroids abolish proinflammatory cytokines release and increase blood IL-10 levels after CPB. Our findings demonstrate a greater release of IL-10 induced by steroid pretreatment, and better heart and lung protection after CPB.