Velio Bocci’s research while affiliated with University of Siena and other places

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Publications (96)


Chapter 1 It is Time that Health Authorities Promote the Use of the Ozone as a Biological Modulator in the Treatment of the Chronic Oxidative Stress Diseases
  • Chapter
  • Full-text available

June 2019

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178 Reads

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1 Citation

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Velio Bocci

An unfavorable combination of factors such as a wrong dogma, the fact that ozone is one of the worst troposphere pollutants and past misuse of ozone have led to a poor consideration of ozone therapy. However, basic and clinical work, developed during the last two decades,clarified both the biochemical and molecular mechanisms of action of ozone in biology and medicine. A judicious dose of ozone dissolved in blood immediately triggers a cascade of well defined chemical compounds acting on multiple cellular targets according to well-known biochemical and molecular pathways. Ozone therapy is proving to be very useful in the dry form of age-related macular degeneration (AMD), cardiovascular diseases, chronic obstructive pulmonary disease (COPD), cerebral diseases and healing disorders, where conventional medicine appears insufficient and too expensive. It is time that World Health Authorities abandon prejudice and skepticism and start to take advantage of an integrative medical application able to help the majority of world population.

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

August 2017

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109 Reads

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8 Citations

Journal of Critical Care

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Paola Mancinelli

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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.


Ozone mediators effect on “in vitro” scratch wound closure

August 2016

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57 Reads

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30 Citations

The beneficial effect of low doses of ozone on wound healing has been well documented and attributed mainly to its bactericidal and pro-oxidant properties. Because ozone itself does not penetrate the cells but immediately reacts with polyunsaturated fatty acids, its effects are the results of oxidative mediators. Among the molecule produces by the interaction of ozone with biological systems there are HNE and H2O2. At today, the cellular mechanisms accounting for the positive effects of mild ozonization on wound closure is still largely unexplored. The aim of the present study was to evaluate the effect of different not toxic doses of ozonated saline ranging from 2-300μM, in an in vitro wound scratch model by the use of human keratinocytes. The results showed that ozonated saline is able to improve in vitro wound healing by stimulating cell proliferation as measured by BrdU assay and PCNA protein levels. In order to better elucidate the molecules that play the main role in the beneficial effect of ozonated saline in wound healing, HNE and H2O2 were used alone or in combination to mimic ozonated saline effect. Surprisingly, keratinocytes treated with different doses of HNE and H2O2 did not significantly improve the wound closure, while the combination of the two compounds was able to improve wound closure. In addition Nrf2 pathways was also activated as determined by its translocation to the nucleous and the increased HO1 gene expression. The present work suggests that ozonated saline effect on wound closure is the results of the combination of more molecules among which HNE and H2O2 play a key role.


It is Time That Health Authorities Promote the Use of Oxygen-ozone Therapy as an Integrative Therapy of Orthodox Drugs

August 2015

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284 Reads

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4 Citations

British Journal of Medicine and Medical Research

Ozone is a very reactive gas and is toxic for the respiratory system but, under precise rules, it can be therapeutically useful for human disease with a chronic oxidative stress. An unfavorable combination of factors such as a wrong dogma, the fact that ozone is one of the worst troposphere pollutants and past misuse of ozone have led to a poor consideration of ozone therapy. However, basic and clinical work, developed during the last two decades, clarified both the biochemical and molecular mechanisms of action of ozone in biology and medicine. A judicious dose of ozone dissolved in blood immediately triggers a cascade of well defined chemical compounds acting on multiple cellular targets according to well-known biochemical and molecular pathways. Ozone therapy is proving to be very useful in the dry form of age-related macular degeneration (AMD), cardiovascular diseases, chronic obstructive pulmonary disease (COPD), cerebral diseases and healing disorders, where conventional medicine appears insufficient and too expensive. It is time that World Health Authorities abandon prejudice and skepticism and start to take advantage of an integrative medical application able to help the majority of world population.


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

July 2015

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315 Reads

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43 Citations

Cardiovascular & Hematological Disorders-Drug Targets

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 cascade of compounds generated during ozone interaction in biological aqueous environments.
The inverted U-shaped curve obtained on the basis of the therapeutic effects using an ozone concentration range between 10 and 80 μg/mL of gas per mL of blood, with 100% being the value obtained in basal conditions
Schematic view of a transverse section of the lumbar region. The arrows indicate the three possible routes of O2–O3 administration.
Scheme of the mechanisms for the control of algesic signals. By releasing endorphins (End.), the enkephalinergic interneuron may inhibit the presynaptic connection of a neurocyte (C) of a spinal ganglion, which, under compression of a herniated disc, stimulates the release of substance P (SP). Endorphins can inhibit the transmission of the algesic signal to neuron D (D), hence to the ascending spinal-thalamic fibers. The monoaminergic or serotonergic neuron A (A), as a component of antinociceptive descending fibers, can reinforce the analgesic effect of neuron B (B). Moreover, the localized oxygenation and analgesia are most important because they permit muscle relaxation and vasodilation, thus a reactivation of muscle metabolism, by favoring oxidation of lactate, neutralization of acidosis, increased synthesis of adenosine triphosphate, Ca²⁺ reuptake, and reabsorption of edema.
The usefulness of ozone treatment in spinal pain

May 2015

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1,112 Reads

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118 Citations

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.



The use of alternative approaches, such as caloric restriction, exercise and healthy diet, together with the conventional medical treatments, could be useful to help patients restore and maintain their healthy physiological state. The homeostasis between the oxidant and antioxidant species is frequently perturbed in a number of human pathological conditions. Hence, the integrative approaches, able to re-establish the redox balance, could play a key role in restoring the cellular homeostasis and reduce the side effects of the orthodox medicine.
Nrf2 activation as target to implement therapeutic treatments

February 2015

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264 Reads

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112 Citations

A chronic increase of oxidative stress is typical of serious pathologies such as myocardial infarction, stroke, chronic limb ischemia, chronic obstructive pulmonary disease (COPD), type II-diabetes, age-related macular degeneration leads to an epic increase of morbidity and mortality in all countries of the world. The initial inflammation followed by an excessive release of reactive oxygen species (ROS) implies a diffused cellular injury that needs to be corrected by an inducible expression of the innate detoxifying and antioxidant system. The transcription factor Nrf2, when properly activated, is able to restore a redox homeostasis and possibly improve human health.


A Practical Approach for Restoring Homeostasis in Diseases Characterized by a Chronic Oxidative Stress

January 2015

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365 Reads

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7 Citations

Journal of Advances in Medical and Pharmaceutical Sciences

The leading cause of death across the globe is due to cardiovascular diseases complicated by a chronic oxidative stress only partially corrected with orthodox drugs. About 80% of deaths occur in low and middle-income countries of every continent. In order to reduce the burden of these diseases, it appears indispensable to integrate orthodox drugs with novel approaches capable of stimulating the natural defense system, which are able to restore homeostasis. Several approaches have been and ozone therapy has been selected because particularly effective.


It is time to integrate conventional therapy by ozone therapy in type-2 diabetes patients

December 2014

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41 Reads

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6 Citations

Annals of Translational Medicine

We read the article written by Gregg et al. [2014] (1). It is an excellent paper and describes that rates of type-2 diabetes related complications have deeply declined during the last fifteen years in spite of a tripled increase of the number of diabetic patients. The reduction of acute myocardial infarction, stroke, amputation and end-stage renal disease are certainly due to an improved clinical care, performance of the healthcare system, and patient education in disease management. A far more effective glycemic control, the use of statins as well as coronary revascularization have been the most critical factors but nonetheless acute myocardial infarction, death from hyperglycemia, stroke and amputation the frequency of which halved remain the most stubborn affections dominated by a chronic oxidative stress. This is due to an increased production of reactive oxygen species (ROS), a decreased GSH synthesis, a decreased antioxidant system, production of phase 2 enzymes and HO-1 incapable of neutralizing the excess of oxidants (2).


Citations (88)


... When used topically, ozonated oils may have anti-inflammatory qualities that can help relieve inflammation and pain. They are thought to influence the release of pro-inflammatory mediators [33]. Ozonated oils are supposed to increase oxygen flow to tissues, potentially improving the body's healing ability. ...

Reference:

Comparative evaluation of the efficacy of topical ozonated olive oil and topical chlorohexidine gluconate in the management of recurrent aphthous stomatitis
The Ozone Paradox: Ozone Is a Strong Oxidant asWell as a Medical Drug

Medicinal Research Reviews

... In these cases, reduced IL-10 was observed [12]. Given that hypoxia reduces IL-10 [13] and IL-10 has the function of downregulating Vascular Endothelial Growth Factor (VEGF) [14], initially decreased IL-10 leads to increased expression of VEGF, contributing to the complications described earlier. Understanding the intricate relationships and signalling pathways involving these molecular effectors is essential not only for unravelling the molecular underpinnings of hypoxia but also for paving the way towards novel therapeutic interventions for patients with Fontan circulation. ...

Hypoxia affects cytokine production and proliferative responses by human peripheral mononuclear cells
  • Citing Article
  • December 1997

Journal of Cellular Physiology

... 14,15 The increased insulin requirement under ventilator and ECMO management in the present study may indicate the involvement of cytokine storms. 16 However, the indicators of a cytokine storm, such as tumor necrosis factor-α, interferon, interleukin (IL)-1β, monocyte chemoattractant protein-1 ...

Reduction of non-enzymatic antioxidants in plasma during ECMO-treatment in ARDS by influence A H1N1
  • Citing Article
  • August 2017

Journal of Critical Care

... Scientific evidence [1] supports various properties of ozone, including its effectiveness as a disinfectant, oxygen donor, immunomodulator, inducer of antioxidant enzymes, metabolic enhancer, and inducer of endothelial nitric oxide synthase. However, it is crucial to acknowledge that ozone, despite its beneficial properties, has inherent toxicity and poses respiratory hazardous risks. ...

The Clinical Application of Ozonetherapy
  • Citing Chapter
  • January 2011

... Nonetheless, its stimulation of the Nrf2 pathway mitigates this reaction, resulting in the transcription of anti-inflammatory genes and diminishing collateral tissue damage. Moreover, O 3 activates growth factors such as Vascular Endothelial Growth Factor (VEGF) and Transforming Growth Factor Beta (TGF-β), facilitating angiogenesis, collagen synthesis, and extracellular matrix creation, which are critical for wound healing and the regeneration of periodontal tissues [41]. Through the activation of essential pathways of signaling, such as the Nrf2, ozone regulates the transcription of genes involved in oxidative stress response, inflammation, and tissue repair. ...

Ozone mediators effect on “in vitro” scratch wound closure
  • Citing Article
  • August 2016

... Interestingly, ozonated saline is an efficient irrigation solution for minimizing abscess development compared to regular saline solution and saline-cephalothin irrigation in treating fecal peritonitis in rats [19]. It was noted that rectal insufflation, as opposed to intravenous and intramuscular methods, was the least unpleasant, safest, and most practical way for administering ozone to 72 non-diabetic individuals with vascular occlusion due to atherosclerosis [20]. ...

The Actual Six Therapeutic Modalities
  • Citing Chapter
  • September 2010

... By doing so, ozone therapy is administered in various acute and chronic musculoskeletal disorders such as fractures [4][5][6], osteoarthritis (OA) [7][8][9][10], low back ache [11,12], osteomyelitis [13][14][15][16], and chronic pain syndromes [17][18][19]. Beyond orthopaedic applications, ozone therapy has shown potential in treating conditions such as chronic fatigue syndrome (CFS) and myalgic encephalomyelitis (ME) using different modalities such as ozonated water, ozone oil, and ozone gas [20][21][22][23][24]. Tailored routes of administration, ranging from enteral ozonated oil [ingestion], enteral ozonated water [ingestion], parenteral oxygen/ozone gas mixture [intramuscular, subcutaneous, intratonsillar, intrathecal, intraperitoneal, periganglionic, intraforaminal, paravertebral, intra-articular, intradiscal, oral submucous, supralaminar, epidural, penile, and intravenous], parenteral ozonated water [intra-tumoral], systemic [minor autohemotherapy (MiAH), major autohemotherapy (MAH), extracorporeal blood oxygenation and ozonation (EBOO), intravenous, and rectal insufflation], topical ozonated water [wound wash, ozonized balneotherapy, mouth wash, irrigation (nasal, sinus, otological, vaginal, intrauterine, intestinal, and intravesical), and sauna therapy, topical oxygen/ ozone gas mixture [insufflation (ontological, intrafistula, intrauterine, and intravesical) and hyperbaric bagging], topical ozonated oil [embrocation and inhalation], and topical ozonated saline solution [wound wash, mouth wash, irrigation (saline, ontological, vaginal, intrauterine, and intravesical)], highlight its versatility [18,[25][26][27]. ...

The Potential Toxicity of Ozone: Side Effects and Contraindications of Ozonetherapy
  • Citing Chapter
  • September 2010

... After innumerable M-AHT in patients with various chronic diseases maintained by chronic oxidative stress, it has become imperative to measure how many ozone molecules added to an adequate volume of blood are necessary to elicit a mild but sufficient acute oxidative stress necessary for developing a tolerable acute oxidative stress which will act as the crucial stimulus for reactivating and upregulating the body's antioxidant system [73]. This concept explains why ozone therapy is becoming an essential integrative system able to restore a normal redox system in numerous clinical applications. ...

The Still Uncertain Future of Ozone Therapy in Medicine
  • Citing Chapter
  • September 2010

... The anti-inflammatory and antioxidant properties of ozone therapy may help in limiting disease progression by reducing oxidative stress and inflammation in MD patients. Ozone therapy also helps in mobilization of stem cells and homing of stem cells toward injured/ischemic sites, thus, aid in tissue repair [152]. This evidence suggests that stem cell therapy in combination with ozone therapy may show better therapeutic efficacy in MD patients. ...

Is Ozone Really a “Wonder Drug”?
  • Citing Chapter
  • September 2010