Bocci V; Borrelli E; Valacchi G; Luzzi E
Quasi-total-body exposure to an oxygen-ozone mixture in a sauna cabin.
Institute of General Physiology, University of Siena, Via Laterina 8,
I-53100 Siena, Italy. fisgen@unisi.it
Eur J Appl Physiol 1999 Nov-Dec;80(6):549-54
Unique Identifier: MEDLINE 20009374

Abstract: 
We have investigated the effects of quasi-total-body exposure of
healthy volunteers to either an oxygen-ozone 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
significant 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 modifier. However, in
the present study no adverse effects were noted after one session.

Di Paolo N; Bocci V; Garosi G; Borrelli E; et al
Extracorporeal blood oxygenation and ozonation (EBOO)
in man. preliminary report [In Process Citation]
Nephrology and Dialysis Department,
Azienda Ospedaliera Senese, Siena, Italy.
Int J Artif Organs 2000 Feb;23(2):131-41
Unique Identifier: MEDLINE 20203854

Abstract: 
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.

Bocci V; Di Paolo N; Garosi G; Aldinucci C; et al
Ozonation of blood during extracorporeal circulation. I.
Rationale, methodology and preliminary studies.
Institute of General Physiology, University of Siena, Italy.
fisgen@unisi.it
Int J Artif Organs 1999 Sep;22(9):645-51
Unique Identifier: MEDLINE 20000235

Abstract: 
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 microg/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 countercurrent with respect to blood and the
time necessary for perfusion in vivo. The biochemical parameters
showed that an O3 concentration as low as 10 microg/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 microg/ml) but the exchanger became less
effective (low pO2 values) due to progressive clogging with cells.

Bocci V
Autohaemotherapy after treatment of blood with ozone. A reappraisal.
Institute of General Physiology, University of Siena, Italy.
J Int Med Res 1994 May-Jun;22(3):131-44
Unique Identifier: MEDLINE 94374551

Abstract: 
Autohaemotherapy, involving bland treatment ex vivo of blood with
ozone and prompt reinfusion into the donor, is a procedure mainly
performed in central Europe, which is claimed to have therapeutic
value in circulatory disorders, viral diseases and cancer. This
practice is mostly performed in private clinics, and good clinical
trials have not been published, which has understandably given rise
to prejudice and scepticism. By analysing possible mechanisms of
action and current hypotheses, this report attempts to explain how
this procedure can be useful in such disparate diseases. The current
state of the art is presented objectively, the lack of toxicity is
documented, and the rationale and therapeutic advantages are
discussed, with the aim of eliciting interest in carrying out
controlled clinical trials.

ADAPTIVE EFFECTS OF OZONE:

Barber E; Menendez S; Leon OS; Barber MO; et al
Prevention of renal injury after induction of ozone tolerance
in rats submitted to warm ischaemia.
Institute of Basic and Preclinical Sciences
Victoria de Giron, Havana, Cuba.
Mediators Inflamm 1999;8(1):37-41
Unique Identifier: MEDLINE 20166854

Abstract: 
On the basis that ozone (O3) can upregulate cellular antioxidant
enzymes, a morphological, biochemical and functional renal study was
performed in rats undergoing a prolonged treatment with O3 before
renal ischaemia. Rats were divided into four groups: (1) control, a
medial abdominal incision was performed to expose the kidneys; (2)
ischaemia, in animals undergoing a bilateral renal ischaemia (30
min), with subsequent reperfusion (3 h); (3) O3 + ischaemia, as group
2, but with previous treatment with O3 (0.5 mg/kg per day given in
2.5 ml O2) via rectal administration for 15 treatments; (4) O2 +
ischaemia, as group 3, but using oxygen (O2) alone. Biochemical
parameters as fructosamine level, phospholipase A, and superoxide
dismutases (SOD) activities, as well as renal plasma flow (RPF) and
glomerular filtration rate (GFR), were measured by means of plasma
clearance of p-amino-hippurate and inulin, respectively. In
comparison with groups 1 and 3, the RPF and GFR were significantly
decreased in groups 2 and 4. Interestingly, renal homogenates of the
latter groups yielded significantly higher values of phospholipase A
activity and fructosamine level in comparison with either the control
(1) and the O3 (3) treated groups. Moreover renal SOD activity showed
a significant increase in group 3 without significant differences
among groups 1, 2 and 4. Morphological alterations of the kidney were
present in 100%, 88% and 30% of the animals in groups 2, 4 and 3,
respectively. It is proposed that the O3 protective effect can be
ascribed to the substantial possibility of upregulating the
antioxidant defence system capable of counteracting the damaging
effect of ischaemia. These findings suggest that, whenever possible,
ozone preconditioning may represent a prophylactic approach for
minimizing renal damage before transplantation.

Leon OS; Menendez S; Merino N; Castillo R; et al
Ozone oxidative preconditioning: a protection against
cellular damage by free radicals.
Center for Research and Biological Evaluation
(Pharmacy Institute of Havana University), Cuba.
ozono@infomed.sld.cu
Mediators Inflamm 1998;7(4):289-94
Unique Identifier: MEDLINE 99006826

Abstract: 
There is some anecdotal evidence that oxygen-ozone therapy may be
beneficial in some human diseases. However so far only a few
biochemical and pharmacodynamic mechanisms have been elucidated. On
the basis of preliminary data we postulated that controlled ozone
administration would promote an oxidative preconditioning preventing
the hepatocellular damage mediated by free radicals. Six groups of
rats were classified as follows: (1) negative control, using
intraperitoneal sunflower oil; (2) positive control using carbon
tetrachloride (CCl4) as an oxidative challenge; (3) oxygen-ozone,
pretreatment via rectal insufflation (15 sessions) and after it,
CCl4; (4) oxygen, as group 3 but using oxygen only; (5) control
oxygen-ozone, as group 3, but without CCl4; group (6) control oxygen,
as group 5, but using oxygen only. We have evaluated critical
biochemical parameters such as levels of transaminase,
cholinesterase, superoxide dismutase, catalase, phospholipase A,
calcium dependent ATPase, reduced glutathione, glucose 6 phosphate
dehydrogenase and lipid peroxidation. Interestingly, in spite of CCl4
administration, group 3 did not differ from group 1, while groups 2
and 4 showed significant differences from groups 1 and 3 and
displayed hepatic damage. To our knowledge these are the first
experimental results showing that repeated administration of ozone in
atoxic doses is able to induce an adaptation to oxidative stress thus
enabling the animals to maintain hepatocellular integrity after CCl4
poisoning.

Bocci V
Ozontherapy as a Possible Biological Response Modifier in Cancer.
Forsch Komplementarmed 1998 Apr;5(2):54-60
Unique Identifier: MEDLINE No Cit. ID Assigned

Bocci V
Ozone as a bioregulator. Pharmacology and toxicology
of ozonetherapy today [see comments]
Institute of General Physiology, University of Siena, Italy.
J Biol Regul Homeost Agents 1996 Apr-Sep;10(2-3):31-53
Unique Identifier: MEDLINE 97394557
Comment in: J Biol Regul Homeost Agents 1996 Apr-Sep;10(2-3):29

Abstract: 
The disinfectant activity of ozone is well recognized and ozone is
used worldwide for sterilization of water. The use of ozone as a
complementary medical approach is less known, because it has mostly
been used in an empirical fashion without a rational basis and
appropriate controls. In spite of this drawback, the use of judicious
and standardized ozone dosages can elicit the formation of ROS acting
as natural physiological activators of several biological functions.
There is now a reasonable understanding of a few mechanisms of action
and, using classical pharmacological concepts, it appears possible to
formulate a rationale for optimizing clinical applications. A further
exciting development is that ozone, being an oxidizer, can upregulate
the intracellular anti-oxidant enzymes eventually inhibiting the
constant, life-long oxidative stress responsible for degenerative
diseases and aging. Among various routes for the administration of
ozone, the autohemotransfusion procedure, consisting in exposing
blood to ozone, i.e. to a calculated and brief oxidative stress,
appears safe, simple, inexpensive and amenable to be adjusted to
different pathological states It is hoped that this review will help
to dispel prejudices, to clarify that ozone toxicity can be tamed, to
show that ozone can act as a bioregulator and to encourage controlled
clinical investigations to evaluate definitely the validity of
ozonetherapy.

Bocci V
Does ozone therapy normalize the cellular redox balance?
Implications for therapy of human immunodeficiency virus
infection and several other diseases.
Institute of General Physiology; University of Siena, Italy.
Med Hypotheses 1996 Feb;46(2):150-4
Unique Identifier: MEDLINE 96231367

Abstract: 
The role of ozone on earth is controversial, as in the stratosphere it
is protective against excessive ultra violet irradiation, and in the
troposphere it is toxic for animals and plants. The effectiveness of
ozone against pathogens is well recognized and ozone appears to be
the best agent for sterilization of water. In spite of this, the use
of ozone in medicine has been overlooked or despised, mostly because
it has been either misused or used without appropriate controls.
Studies carried out in our laboratory have revealed that ozone can
display relevant biological effects and that, having defined its
therapeutic index, can become an important and reliable drug for the
treatment of several diseases. An exciting new aspect is that ozone,
being a strong oxidizer, can stimulate the increase of cellular
anti-oxidant enzymes, eventually inhibiting the oxidative stress.

Bocci V
Ozonization of blood for the therapy of viral diseases
and immunodeficiencies. A hypothesis.
Institute of General Physiology and Nutritional Sciences,
University of Siena, Italy.
Med Hypotheses 1992 Sep;39(1):30-4
Unique Identifier: MEDLINE 93062268

Abstract: 
In the last 3 decades major autohemotherapy after exposure to ozone
has been used in Europe in uncontrolled trials carried out in
patients with many illnesses, particularly chronic viral diseases and
neoplasms. It appears that the treatment may activate the host's
immune system by inducing the production of immunoactive cytokines
and it may now be possible to rationalize the procedure, improve the
regimen and assess the outcome. It is apparent, however, that such a
therapeutic approach, in order to be acceptable, requires an
investigative effort of biologists and clinicians. Once this is done,
owing to the large range of medical applications and the simplicity
of the procedure, autohemotherapy could become very valuable
particularly in underdeveloped countries.