Emma Borrelli

Plasma concentrations of cytokines, their soluble receptors, and antioxidant vitamins can predict the development of multiple organ failure in patients at risk

OBJECTIVES The aims of this study were: a) to evaluate plasma concentrations of cytokines and their soluble receptors, as well as antioxidant substances in patients at high risk of developing multiple organ failure; b) to investigate early change: and c) to examine the possible prognostic value of these elements. DESIGN Prospective analysis. SETTING Surgical intensive care unit (ICU) of a university hospital. PATIENTS sixteen patients at risk for multiple organ failure. MEASUREMENTS AND MAIN RESULTS Ten patients developed multiple organ failure and five of them died. Whereas tumor necrosis factor-alpha (TNF-alpha) plasma concentrations were only borderline higher in patients developing multiple organ failure, TNF-soluble receptors 55 and 75 were significantly increased during all ICU days compared with patients not going into organ failure. Interleukin-6 plasma concentrations were higher in patients developing multiple organ failure during the first 2 days after ICU admission. The antioxidant vitamin C was significantly decreased in patients going into multiple organ failure during all ICU days. Other biochemical markers of antioxidant activity, such as vitamin E, copper, and zinc plasma concentrations, did not differ between the two groups. CONCLUSIONS Our data suggest that there is a marked increase in anti-TNF activity and a decrease of antioxidant defense in patients at risk of developing multiple organ failure. The predictive value of plasma concentrations of circulating TNF-soluble receptors and vitamin C in this type of patient needs further evaluation.

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.

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.

Ozone In Medicine

Abstract Ozone therapy has been used as a complementary medical approach for half a century but it has encountered skepticism by orthodox medicine because, particularly in the past, it has been used by practitioners and others without a rational basis and appropriate controls. With the advent of modern medical ozone generators incorporating a photometer, it has become possible to obtain precise ozone concentrations and to evaluate some mechanisms of action and possible toxicity. In contrast with the respiratory tract, human blood exposed to appropriate ozone concentrations is able to tame its strong oxidant properties and neither acute, nor chronic side effects have ensued in millions of patients treated with ozonated autohaemotherapy (O3-AHT). This review summarizes our studies aimed at clarifying biological effects, defining any possible damage, the therapeutic window and suitable doses able to express a therapeutic activity. A very interesting and promising aspect is the induction of the so-called heat stress proteins (HSP) leading to adaptation to a chronic oxidative stress. The use of ozone in human therapy has been reviewed but so far very few controlled clinical studies have been reported. Mostly on the basis of anecdotal results, ozone therapy appears useful in infectious diseases, immune depression, vascular disorders, degenerative diseases and orthopedics.

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

Abstract We have investigated the effects of quasi-total-body exposure of healthy volunteers to either an oxygen-ozone mixture (O2-O3) or to oxygen (O2) 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 significant variations of body temperature, venous partial pressure of O2 values, TBARS and plasma levels of interleukin 8, particularly after O2-O3 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 O2 species, which should be considered if this approach is to be used as a biological response modifier. However, in the present study no adverse effects were noted after one session.

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.

Extracorporeal blood oxygenation and ozonation (EBOO) in man. preliminary report.

Autohemotherapy with ozone has been used for four decades with encouraging results but, owing to the lack of clinical studies, it has never been adopted by orthodox medicine. Confident of the valid principles of ozone therapy, we have endeavoured to increase its therapeutic efficacy. Over a ten-year period we have developed an apparatus that makes it possible to treat large quantities of blood with ozone in extracorporeal circulation (extracorporeal blood oxigenation and ozonation EBOO). One of us volunteered to test the system and after six treatments noted the disappearance of two lipomas. This prompted us to treat a patient with Madelung disease and several patients with atherosclerotic vasculopathy. Besides showing therapeutic effects, the preliminary results indicate that EBOO is clinically valid, without side-effects and worthy of testing in various diseases.

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.

Ozonation of blood during extracorporeal circulation. I. Rationale, methodology and preliminary studies.

We investigated whether exposure of blood ex-vivo to oxygen-ozone (O2-O3) through a gas exchanger is feasible and practical. We first evaluated the classical dialysis-type technique but we soon realized that semipermeable membranes are unsuitable because they are hydrophilic and vulnerable to O3. We therefore adopted a system with hydrophobic O3-resistant hollow fibers enclosed in a polycarbonate housing with a membrane area of about 0.5 m2. First we tested the system with normal saline, determining the production of hydrogen peroxide (H2O2) at O3 concentrations from 5 to 40 μg/ml. We then evaluated critical parameters by circulating swine blood in vitro; this revealed that heparin is not an ideal anticoagulant for this system. Finally, we performed several experiments in sheep and defined optimal anticoagulant dose (sodium citrate, ACD), priming solution, volume of blood flow per min, volume and concentration of O2-O3 mixture flowing counter-current with respect to blood and the time necessary for perfusion in vivo. The biochemical parameters showed that an O3 concentration as low as 10 μg/ml is effective; this means that gas exchange and O3 reactivity are rapid and capable of inducing biological effects. The sheep showed no adverse effects even after 50 min of extracorporeal circulation at higher O3 concentrations (20 to 40 μg/ml) but the exchanger became less effective (low pO2 values) due to progressive clogging with cells.

Inhibition by methylprednisolone of leukocyte-induced pulmonary damage.

Background and MethodsThe 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. ResultsIntraperitoneal 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. ConclusionsThe 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. (Crit Care Med 1991; 19:260)