*Corresponding author: Emma Borrelli Department of Medical Biotechnologies, University of Siena, Italy ISSN: 0976-3031 RESEARCH ARTICLE OXYGEN OZONE THERAPY IN THE INTEGRATED TREATMENT OF CHRONIC ULCER: A CASE SERIES REPORT Emma Borrelli 1 , Amato De Monte 2 and Velio Bocci 3 Received 5th, April, 2015 Received in revised form 12th, April, 2015 Accepted 6th, May, 2015 Published online 28th, May, 2015 Copyright © Emma Borrelli et al., This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. INTRODUCTION Chronic ulcers (CU) present a major challenge to health care systems worldwide. In the United States alone, these wounds affect an estimated 2.5–4.5 million people (1). Predominantly a condition of the elderly, chronic leg and foot ulcers will continue to become more prevalent as the world population ages. The vascular etiology of CU include the venous stasis, arterial occlusive disease, thromboangioitis obliterans and lymphedema. Vasculitic causes of leg ulcers are leukocytoclastic vasculitis, autoimmune disease-related vasculitis, polyarteritis nodosa and Wegener’s granulomatosis. Other causes of non healing ulcerations may be neoplastic diseases (for example leukemia cutis, lymphoma or primary skin neoplasms), traumatically-induced wounds, infectious wounds (with primary or secondary bacterial, fungal, viral, mycobacterial or parasitic etiology),hemathologic diseases (anti-phospholipid antibody syndrome or cryoglobulinemia) and metabolic diseases such as diabetes and gout(2). The most frequent site of ulceration is in the gaiter area, followed by the calf and the foot (3). Chronic ulcers are associated with high treatment costs, decreased quality of life, and are a significant cause of morbidity. A frequent and distressing problem is the overwhelming rate of recurrence and the duration of the ulcer diathesis. Fittingly, the problem of chronic wounds has been defined as “The Silent Epidemic” (Smith & Nephew Foundation). Clinical Hystory of CU The duration of an ulcer varies from about nine months to a few years. This depends upon the age of the patient, the pathology, the side, the site of ulceration and the efficacy of the therapy. Nelson (4) examined 101 systematic reviews and observational studies and evaluated the quality of evidence for interventions. Topical antimicrobial agents, surgical and enzymatic debriding agents (5), collagen or alginate dressings, intermittent pneumatic compression, topically applied mesoglycan, keratinocyte growth factor 2 and topical negative pressure were included as approaches of variable effectiveness. Oral pentoxifylline(6), flavonoids, systemic mesoglycan and iontophoretic administration of calcitonin peptide(7) were likely to be beneficial. Unknown effectiveness was attributed to oral aspirin(8), sulodexide(9) , cultured allogenic dermal replacement, low level laser treatment, IV prostaglandin E1, oral rutosides, skin grafting, therapeutic ultrasound, oral thromboxane alpha 2 antagonists, zinc, silver treatment(10) and larval therapy. Other approaches such as light and magnetic therapies, topical warming-cooling and hypoclorous acid were only mentioned. It appears that so far a really effective method able to achieve healing and prevent recurrence is not available. A new approach to the management of CU In Germany and Italy, from 2006, many leg ulcers have been successfully treated with the ozonated autohaemotherapy (O 3 - AHT) (11-13). It has taken several years to clarify the biochemical, molecular and pharmacologic events. It is useful to say that ozone is ten-fold more soluble in the water of plasma than oxygen: this fact implies that mixing human blood with an equivalent volume of a gas mixture composed of about 96% O2 and 4% O3 leads to a very rapid solubilization of ozone, which, owing to its high reactivity (E°= +2,076 V), reacts with hydrosoluble plasma antioxidants (ascorbic acid, uric acid, trace of reduced glutathione) and with the unsaturated lipids carried out by albumin as follows: R-CH = HC-R + O 3 + H 2 O → H 2 O 2 + 2 R-CHO This means that in a few minutes all the ozone dose is exhausted because it completely reacts and generates its messengers such as hydrogen peroxide and aldehydes derived from the unsaturated fatty acids peroxidation. The formation of aldehydes leads to the final formation of alkenals such as trans- 4-hydroxy-2-nonenal (4-HNE from n-6) and a small quantity of trans-4-hydroxy-2-hexenal (from n-3)(14) Consequently ozone acts simply as a pro-drug and generates these two messengers. The unionized hydrogen peroxide immediately enters into the mass of erythrocytes and activates glycolysis with ATP increase and, most important, enhances the production of 2,3 di-phospho-glygerate (2,3-DPG), which is able to shift to the right the oxyhemoglobin dissociation curve, thus increasing the release of oxygen in the ischemic areas such as the ulcer’s area (15). Moreover the infusion of ozonated blood implies an activation of nitric oxide release by the endothelium (16). Available Online at http://www.recentscientific.com International Journal of Recent Scientific Research International Journal of Recent Scientific Research Vol. 6, Issue, 5, pp.4132-4136, May, 2015