Emma Borrelli

University of Siena / Università di Siena, Preventive medicine, Department Member

University of Siena / Università di Siena, Medical Biotechnologies, Department Member

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Consultant Pulmonologist, Preventive Medicine Unit, University Hospital.
Adjunct Professor, Postgraduate Course on Oxygen Ozone therapy, University of Siena.
Director, Laboratory of Oxidative Stress.
Prof. Velio Bocci’s Assistant
Supervisors: Prof. Velio Bocci

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Papers by Emma Borrelli

Relationship between cardiac index (CI) and cytokine production after cardiopulmonary bypass (CPB)

Critical Care Medicine, 2000

IDS Number: 388ZD Subject Category: Critical Care Medicine Publisher: LIPPINCOTT WILLIAMS & W... more

The Importance of the Redox Modulation in the Prevention and Treatment of Chronic Pulmonary Diseases

Biochemistry, Dec 6, 2022

This chapter discusses the most important mechanisms of action of oxidants in the pathogenesis of... more This chapter discusses the most important mechanisms of action of oxidants in the pathogenesis of chronic pulmonary oxidative diseases and the possible use of redox modulators in the prevention and treatment of oxidant/antioxidant intracellular imbalance. Recent acquisitions on cellular physiology reported the key role, in micromolecular doses, of reactive oxygen species (ROS) as signaling molecules although excessive ROS contribute to the development and progression of a large spectrum of diseases, including chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Therefore, a correct understanding of the roles of redox regulation in the respiratory system during the impairment of oxidative balance and the subsequent development of chronic lung diseases appears to be important. Moreover, an interdependence between oxidant and inflammatory mediators has been shown in several experimental studies on chronic lung diseases, making more intriguing the comprehension of the pathophysiological phenomena and the therapeutic approach. This chapter discusses the role of various exogenous substances targeting oxidant/ antioxidant balance in the treatment of COPD and IPF and their very limited beneficial effects due to the reduced bioavailability in the human body. Finally, the importance of novel routes of administration or a combination of redox modulators will be discussed as a promising avenue for the prevention and treatment of this common and highly disabling disease.

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The Problem of Chronic Oxidative Stress and the Systemic Indirect Ozone Therapy as a Possible Solution

Book Publisher International (a part of SCIENCEDOMAIN International), Mar 5, 2021

Treatment of advanced non-small-cell lung cancer with oxygen ozone therapy and mistletoe: an integrative approach

European Journal of Integrative Medicine, Sep 1, 2012

Background. Treatment options for advanced nonsmall-cell lung cancer are inadequate. There remain... more Background. Treatment options for advanced nonsmall-cell lung cancer are inadequate. There remains a critical need for more effective systemic therapies. Forty-one patients with advanced nonsmall-cell lung cancer were treated on a 28-day cycle with a very high-dose, cisplatin-based three-drug regimen. A treatment cycle consisted of an intravenous (IV) injection of cisplatin 100 mg/m2 on days 1 and 8; etoposide 60 mg/m2 IV over 30 minutes on days 1, 2, 8, and 9 (cycles 1 and 3 only); and mitomycin C 8 mg/mz IV bolus on day 1 (cycles 2 and 4 only) (PEM regimen). The median dose intensity of cisplatin delivered was 49 mg/mz/wk, or 98% of the planned dose. One patient achieved a complete response and 16 patients a partial response or regression, yielding an overall objective response rate of 41%. The median duration of response was 21 weeks. Median survival of all patients was 38 weeks. Neurologic toxicity was dose limiting. The frequency of peripheral neuropathy and ototoxicity was directly related to cumulative cisplatin dose. In five patients, a progressive peripheral neuropathy developed after discontinuation of cisplatin. Hematologic toxicity also was significant. Conclusions. This very high-dose, cisplatin-based chemotherapy regimen has appreciable activity in ad-Methods. Results.

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Extracorporeal life support in COVID‐19‐related acute respiratory distress syndrome: A EuroELSO international survey

Artificial Organs, 2021

Extracorporeal life support (ECLS) is a means to support patients with acute respiratory failure.... more Extracorporeal life support (ECLS) is a means to support patients with acute respiratory failure. Initially, recommendations to treat severe cases of pandemic coronavirus disease 2019 (COVID‐19) with ECLS have been restrained. In the meantime, ECLS has been shown to produce similar outcomes in patients with severe COVID‐19 compared to existing data on ARDS mortality. We performed an international email survey to assess how ECLS providers worldwide have previously used ECLS during the treatment of critically ill patients with COVID‐19. A questionnaire with 45 questions (covering, e.g., indication, technical aspects, benefit, and reasons for treatment discontinuation), mostly multiple choice, was distributed by email to ECLS centers. The survey was approved by the European branch of the Extracorporeal Life Support Organization (ELSO); 276 ECMO professionals from 98 centers in 30 different countries on four continents reported that they employed ECMO for very severe COVID‐19 cases, mos...

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Integration of the oxygen–ozone therapy in the treatment of dry age-related macular degeneration: a randomised controlled study

European Journal of Integrative Medicine, Sep 1, 2012

Ozonation of Blood during Extracorporeal Circulation II. Comparative Analysis of Several Oxygenator-Ozonators and Selection of One Type

International Journal of Artificial Organs, Dec 1, 2001

Exposure of human blood ex vivo to oxygen-ozone (O 2-O 3) using either dialysis exchangers or nor... more Exposure of human blood ex vivo to oxygen-ozone (O 2-O 3) using either dialysis exchangers or normal oxygenators gives rise to a number of problems, one of which linked to platelet activation, leads to rapid occlusion and no gas exchange. Semipermeable membranes were found unsuitable because, except for one, they were gas-transfer inefficient, allowed ultrafiltration and were more or less vulnerable to O 3. Over the last three years we have examined several types of hydrophobic O 3-resistant hollow fiber capillaries but, if the polypropylene surface is not properly coated, there is platelet aggregation and blood coagulation. These problems while far less relevant with O 2 alone, become prohibitive in the presence of ozone. Recently new oxygenators have been prepared with special materials to make them more biocompatible and it has become possible to oxygenate and ozonate up to 5L of blood in about an hour, thus making the treatment of critical patients feasible.

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Inhibition of CD11-CD18 Complex Prevents Acute Lung Injury and Reduces Mortality after Peritonitis in Rabbits

American Journal of Respiratory and Critical Care Medicine, Mar 1, 2000

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

PubMed, 2012

Aim: To evaluate the effect of systemic ozonated major autohaemotherapy (O(3)-AHT) in patients af... more 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.

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O2 Extraction Ratio (Er) and Cytokine Production During Cardiopulmonary Bypass (CPB)

Critical Care Medicine, Dec 1, 1999

IDS Number: 276RX; Subject Category: Critical Care Medicine; Publisher: LIPPINCOTT WILLIAMS &... more

Ozone: A Multifaceted Molecule with Unexpected Therapeutic Activity

Current Medicinal Chemistry, Feb 4, 2016

The terms and conditions for the reuse of this version of the manuscript are specified in the pub... more The terms and conditions for the reuse of this version of the manuscript are specified in the publishing policy. Works made available under a Creative Commons license can be used according to the terms and conditions of said license. For all terms of use and more information see the publisher's website.

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Oxygen Ozone Therapy in the Treatment of Chronic Obstructive Pulmonary Disease: An Integrative Approach

American Journal of Clinical and Experimental Medicine, 2014

A pilot study has been performed on fifty COPD patients: besides using effective drugs, half of t... more A pilot study has been performed on fifty COPD patients: besides using effective drugs, half of the patients have been treated also with major ozonated autohaemotherapy. This treatment has been evaluated during the last two decades and is absolutely atoxic: the treated patients have shown a significant improvement of the six minute walking test and Saint George Respiratory Questionnaire total score. Surprisingly their quality of life was also much improved. Orthodox medications appears to be greatly potentiated when integrated by the autologous infusion of ozonated blood. This combination deserves to be evaluated in an ample clinical trial.

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Inhibition by methylprednisolone of leukocyte-induced pulmonary damage

Critical Care Medicine, Feb 1, 1991

The purpose of this study was twofold: the development of a chronic model of leukocyte-mediated p... more The purpose of this study was twofold: the development of a chronic model of leukocyte-mediated pulmonary injury and the evaluation of the protective effects of methylprednisolone. Rabbits were inoculated ip with zymosan. Blood gases and circulating leukocytes were evaluated. Survivors were killed on day 10 for microscopic studies and for the evaluation of lung lipid peroxidation through the by-product malondialdehyde. Intraperitoneal zymosan resulted in a marked decrease of Pao2 and circulating leukocytes, and increased cellularity of alveolar septa, interstitial edema, and increased lung malondialdehyde. Pulmonary damage was partially prevented when methylprednisolone was administered before zymosan inoculation, but not when methylprednisolone was given 24 hr later. The authors conclude that a local nonseptic inflammatory stimulus may provoke remote changes to the lungs and that methylprednisolone may counteract the process only if it is administered before or very early after the onset of inflammation.

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

British journal of medicine and medical research, Jan 10, 2015

Ozone is a very reactive gas and is toxic for the respiratory system but, under precise rules, it... more 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. Review Article Bocci and Borrelli; BJMMR, 10(4): 1-9, 2015; Article no.BJMMR.17684 2

Early diagnosis of adult respiratory distress syndrome

Journal of Thoracic Imaging, Jul 1, 1988

This article presents an experimental model of pulmonary injury resembling subclinical human adul... more This article presents an experimental model of pulmonary injury resembling subclinical human adult respiratory distress syndrome (ARDS) mediated by leukocytes. The activation of complement was prolonged by an intraperitoneal injection of a suspension of zymosan in paraffin. The first step in the development of the disease was an accumulation of polymorphonuclear leukocytes in the lungs. No significant changes were observed on chest radiographs or computed tomograms and the pathophysiologic changes were only minimal in spite of the characteristic structural changes. The criteria currently used for the diagnosis of ARDS are not sensitive enough to detect the subclinical phase of the disease.

Quasi-total-body exposure to an oxygen-ozone mixture in a sauna cabin

European journal of applied physiology and occupational physiology, Oct 1, 1999

We have investigated the eects of quasi-totalbody exposure of healthy volunteers to either an oxy... more We have investigated the eects of quasi-totalbody exposure of healthy volunteers to either an oxygenozone mixture (O 2-O 3) or to oxygen (O 2) alone during a short period in a sauna cabin. The subjects underwent both an experimental and a control examination, separated by a 3.5-month interval. Body mass, blood pressure, body temperature changes, electrocardiograms, venous blood gas and haemocytometric analyses, total antioxidant status and plasma levels of protein thiol groups, thiobarbituric acid reactive substances (TBARS), plasma cytokine, hepatic enzymes and creatine were determined before, immediately after the 20-min period in the cabin and then 0.5, 1.0 and 24 h afterwards. We observed statistically signi®cant variations of body temperature, venous partial pressure of O 2 values, TBARS and plasma levels of interleukin 8, particularly after O 2-O 3 exposure. The increase in TBARS plasma levels concomitant with protein oxidation has been tentatively interpreted as being attributable to the transcutaneous passage of some reactive O 2 species, which should be considered if this approach is to be used as a biological response modi®er. However, in the present study no adverse eects were noted after one session.

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Systemic effects after colorectal insufflation of oxygen/ozone in rabbit

urrently, with reappraisal of ozone therapy, it has been utilized worldwide in research and clini... more urrently, with reappraisal of ozone therapy, it has been utilized worldwide in research and clinical field. Most of the studies investigating effects of ozone on blood parameters are conducted by directly ozonating the blood. Rectal insufflation is a simple, easy and inexpensive method of delivering ozone. Little is known how these gases affect some fundamental hemorheologic parameters when given by insufflation. We aimed to investigate the effects of colorectally insufflated oxygen-ozone on red blood cell rheology in rabbits. Rabbits were divided into Group 1 (control); Groups 2, 3 and 4 (oxygen rectally insufflated respectively for 15, 21 and 36 days); Groups 5, 6 and 7 (ozone rectally insufflated respectively for 15, 21 and 36 days). Erythrocyte deformability, aggregation and osmotic fragility were determined from blood samples at the end of each treatment period. Our 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

The Use of Ozone in Medicine

Annals of Medical and Health Sciences Research, 2018

This is an open access article distributed under the terms of the Creative Commons Attribution-No... more This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

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Interferon (Ifn) Levels in Human Pulmonary Tumors

Journal of interferon research, 1989

Das Paradox Ozon: Ozon ist ebenso ein starkes Oxidant wie ein Arzneimittel

Nach fünf Jahrzehnten, gekennzeichnet durch Empirie und einige Fallstricke, sind einige der grund... more Nach fünf Jahrzehnten, gekennzeichnet durch Empirie und einige Fallstricke, sind einige der grundlegenden Mechanismen der Tätigkeit des Ozons in der Lungentoxikologie und in der Medizin geklärt. Das gegenwärtige Wissen ermöglicht es zu erkennen, dass das längere Einatmen von Ozon sehr schädlich sein kann, in erster Linie für die Lunge und danach für den gesamten Organismus. Andererseits kann eine kleine Dosis Ozon, die gut gegen die vorhandene antioxidative Kapazität von Blut kalibriert ist, mehrere nützliche biochemische Mechanismen steuern und das antioxidative System reaktivieren. Genauer gesagt wirkt die Ozontherapie-erstens ex vivo und zweitens während der "Retransfusion" des ozonisierten Blutes, bei der Blutzellen und das Endothel erreicht wird und "Ozonbotenstoffe" auf Milliarden von Zellen übertragen werden, wo sie den therapeutischen Effekt generieren. So können einzelne Ozondosen, trotz eines allgemeinen Vorurteils, therapeutisch bei ausgewählten Erkrankungen des Menschen ohne irgendeine Toxizität oder Nebenwirkungen benutzt werden. Darüber hinaus sind die Vielseitigkeit und die Amplitude der positiven Wirkungen von Ozonanwendungen in der Orthopädie, bei Haut-und Schleimhautinfektionen als auch in der Zahnmedizin , sowie vieler anderer veröffentlichter Indikationen, offensichtlich geworden.

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