Adjunct treatment with ozone to enhance therapy of knee osteoarthritis: preliminary results.

Knee osteoarthritis (knee OA), commonly known as gonarthrosis, is a chronic pathology involving knee at the joint level causing progressive pain, stiffness and difficulty in ambulation and leg movements. So far in situ infiltration therapies such as platelet rich plasma, conditioned autologous serum or hyaluronic acid, provided some encouraging though limited hopes for a routinely recommended therapy for knee OA. Recent clinical successful observations about the use of whole autologous blood ozonated with a calibrated mixture of oxygen and ozone, has promoted the present research study, in order to treat knee OA. A number of 250 patients suffering with knee OA of different Ahlback scores, were treated with infiltration of ozonated blood and evaluated for their WOMAC and Lequesne indexes, pre- and post-treatment, to evaluate pain, disability and stiffness. Patients recovered about 50% of their health status, reducing pain, stiffness and disability by only 5 sessions, one/week, with 20 µg/ml O3 ozonated autologous blood knee infiltrations. The evidence asks for further supporting results yet encourages our efforts to go ahead in this research issue. Key Points •The oxygen-ozone therapy via ozonated blood infiltration was used in this study. •Ozone reduced pain, disability, and stiffness in both female and male patients. •The treatment with ozone improved WOMAC both in type I and type II Ahlback knee OA. •The oxygen-ozone therapy via ozonated blood ameliorated Lequesne functional index.

Ozone in the adjunct medical treatment. The round personality of a molecule with hormetic properties.

Ozone, an allotrope of oxygen, is enjoying an increasing interest in the setting and management of the medical adjunct treatment, which is called, maybe too simplistically, "ozone therapy". Ozone is not a medicine, so the word therapy does not properly fit this gaseous molecule. Like many natural compounds, for example plant flavonoids, even ozone interacts with aryl hydrocarbon receptors (AhRs) and, at low doses, it works according to the paradoxical mechanism of hormesis, involving mitochondria (mitohormesis). Ozone, in the hormetic range, exerts cell protective functions via the Nrf2-mediated activation of the anti-oxidant system, then leading to anti-inflammatory effects, also via the triggering of low doses of 4-HNE. Moreover, its interaction with plasma and lipids forms reactive oxygen species (ROS) and lipoperoxides (LPOs), generally called ozonides, which are enabled to rule the major molecular actions of ozone in the cell. Ozone behaves as a bioregulator, by activating a wide population of reactive intermediates, which usually target mitochondria and their turnover/biogenesis, often leading to a pleiotropic spectrum of actions and behaving as a tuner of the fundamental mechanisms of survival in the cell. In this sense, ozone can be considered a novelty in the medical sciences and in the clinical approach to pharmacology and medical therapy, due to its ability to target complex regulatory systems and not simple receptors.

The Oxygen-Ozone Adjunct Medical Treatment According to the Protocols from the Italian Scientific Society of Oxygen-Ozone Therapy: How Ozone Applications in the Blood Can Influence Clinical Therapy Success via the Modulation of Cell Biology and Immunity.

BACKGROUND: Ozone is an allotrope of oxygen whose use in medicine has rapidly grown in recent years. Ozonated blood allows for the use of ozone in a safe modality, as plasma and blood cells are endowed with an antioxidant system able to quench ozone's pro-oxidant property and to elicit the Nrf2/Kwap1/ARE pathway. METHODS: We present two clinical studies, a case-series (six patients) observational study adopting ozone as a major autohemotherapy and topical ozone to address infected post-surgical wounds with multi-drug resistant bacteria and an observational study (250 patients) using ozonated blood for treating knee osteoarthritis. RESULTS: Ozonated blood via major autohemotherapy reduced the extent of infections in wounds, reduced the inflammatory biomarkers by more than 75% and improved patients' QoL, whereas ozonated blood via minor autohemotherapy improved significantly (p < 0.001) WOMAC and Lequesne's parameters in knee osteoarthritis. CONCLUSIONS: The models described, i.e., ozone autohemotherapy in wound antimicrobial treatment and ozonated blood in knee osteoarthrosis, following our protocols, share the outstanding ability of ozone to modulate the innate immune response and address bacterial clearance as well as inflammation and pain.

The Role of Ozone as an Nrf2-Keap1-ARE Activator in the Anti-Microbial Activity and Immunity Modulation of Infected Wounds.

Ozone is an allotrope of oxygen, widely known to exert an anti-oxidant potential. The ability of low, controlled and standardized doses of ozone in the ozone adjunct treatment of bacterial infections, which occur in wounds, is engaging clinical research to deepen the role of ozone in eradicating even multidrug-resistant bacteria. Ozone activates the nuclear factor erythroid 2-related factor 2 (Nrf2), and this activation triggers a complex cascade of events, which ultimately leads to macrophage training and an improvement in their ability to operate a clearance of bacteria in the patient's anatomical districts. In this review, we try to elucidate the recent evidence about the mechanisms with which ozone can actually remove bacteria and even multi-drug-resistant (MDR) bacteria, accounting on its complex ability in modulating immunity.

Cytokine profiles in COVID-19 patients undergoing adjunct ozone therapy: some comments.

A comment to: Ghaleh HEG, Izadi M, Javanbakht M, Ghanei M, Einollahi B, Jafari NJ, Alishiri G, Aslani J, Abolghasemi H, Simonetti V, Khafaei M, Zhao S, Saadat SH, Ahmadi M, Parvin S, Vazifedoust S, Alvanagh AG. Cytokine profile and antioxidants status in the moderate and severe COVID-19 patients: a trial of ozone therapy impact as a medicinal supplement. Inflammopharmacology. 2023 Jul 12. https://doi.org/10.1007/s10787 -023-01288-9.

The Mito-Hormetic Mechanisms of Ozone in the Clearance of SARS-CoV2 and in the COVID-19 Therapy.

An increasing body of evidence in the literature is reporting the feasibility of using medical ozone as a possible alternative and adjuvant treatment for COVID-19 patients, significantly reducing hospitalization time, pro-inflammatory indicators, and coagulation markers and improving blood oxygenation parameters. In addition to the well-described ability of medical ozone in counteracting oxidative stress through the upregulation of the main anti-oxidant and scavenging enzymes, oxygen-ozone (O2-O3) therapy has also proved effective in reducing chronic inflammation and the occurrence of immune thrombosis, two key players involved in COVID-19 exacerbation and severity. As chronic inflammation and oxidative stress are also reported to be among the main drivers of the long sequelae of SARS-CoV2 infection, a rising number of studies is investigating the potential of O2-O3 therapy to reduce and/or prevent the wide range of post-COVID (or PASC)-related disorders. This narrative review aims to describe the molecular mechanisms through which medical ozone acts, to summarize the clinical evidence on the use of O2-O3 therapy as an alternative and adjuvant COVID-19 treatment, and to discuss the emerging potential of this approach in the context of PASC symptoms, thus offering new insights into effective and safe nonantiviral therapies for the fighting of this devastating pandemic.

COVID-19 Medical and Pharmacological Management in the European Countries Compared to Italy: An Overview.

(1) Background: Italy accounts for more than 150,000 deaths due to the COVID-19 pandemic, leading the top rank in SARS-CoV-2-caused deceases in Europe. A survey on the different ways by which the COVID-19 pandemic emergency was managed in the foreign European countries compared to Italy is the purpose of this paper. (2) Methods: A literature search and various mathematical algorithms to approach a rank scoring scale were used to describe in detail the different approaches used by European countries to manage the COVID-19 pandemic emergency. (3) Results: The study showed that Italy stands at the bottom ranking for COVID-19 management due to its high mortality rate. Possible causes of the observed huge numbers of hospitalization and deaths were (a) the demographic composition of the European country; (b) its decentralized healthcare system organization; (c) the role of correct pharmacology in the early stages before hospitalization. Post-mortem examinations were of paramount importance to elucidate the etiopathogenesis of COVID-19 and to tailor a suitable and proper therapy in the early symptomatic stages of COVID-19, preventing hospitalization. (4) Conclusions: Factors such as the significant impact on elderly people, the public health organization prevalently state-owned and represented mainly by hospitals, and criticism of the home therapy approach toward SARS-CoV-2-infected people, may have concurred in increasing the number of COVID-19 deaths in Italy.

The Problem of Home Therapy during COVID-19 Pandemic in Italy: Government Guidelines versus Freedom of Cure?

After starting in late 2019, COVID-19 spread worldwide, and Italy was one of the first Western nations to be seriously affected. At that time, both the virus and the disease were little known and there were no Evidence-Based Medicine indications for treatment. The Italian Health Ministry guidelines claimed that, unless oxygen saturation fell to <92%, no pharmacological treatment was necessary during the first 72 hours, other than on a purely symptomatic basis, preferably with paracetamol. As later confirmed, that delay in therapeutic intervention may have been responsible for numerous hospital admissions and a very high lethality (3.5 %). To try to remedy this situation, several volunteer groups were formed, managing to promptlycure thousands of patients at home with non-steroidal anti-inflammatory drugs and a variety of re-purposed drugs (principally hydroxychloroquine, ivermectin) and supplements (such as antioxidants, polyphenols and vitamin D). Although not documented by any randomized controlled studies, these approaches were nonetheless based on the best available evidence, were aimed at addressing otherwise unmet major needs and produced a significant reduction of hospitalizations, of symptom duration, and a complete recovery from the disease compared with late treatment, according to some retrospective observational studies and the clinical experience of many physicians. A prompt discussion, with a clear and open exchange between healthcare Institutions and the said groups of voluntary physicians, could clarify the most effective approaches to reduce the number of hospitalizations and the lethality of this disease.