We obtained extremely good results regarding Herpes labialis in women: the good trick is to apply the ozonated oil as soon as the patient recognizes the prodromal symptoms. Chronic viral, bacterial, and parasitic diseases such as hepatitis B and C, HIV-AIDS, HPV, tuberculosis, gastro-intestinal infections, malaria, toxoplasmosis, listeriosis, amebiasis, leishmaniasis, Chagas disease and the seven tropical diseases affect almost two billion people and strikingly reduce the life span (Finch, 2009). Preliminary report. IPF and asthma have been also characterized by dysimmunity, with a prevalent Th1>Th2-like cytokine pattern in IPF (Keane and Strieter, 2002) and a Th2>Th1-like pattern in asthma (Robinson et al., 1993; OByrne et al. Thomas T., Thomas G., McLendon C., Sutton T., Mullan M. Beta-Amyloid-mediated vasoactivity and vascular endothelial damage. Indeed, around one in five people (frequent in children and women), or about ten million adults in the UK report each year the incidence of small, painful sores occurring on the tongue, lips and cheeks. Extra guests are at the hotels discretion and may be subject to additional fees. Forman H. J., Fukuto J. M., Miller T., et al. Familiarity (hence, genetic factors), age and sex and an extremely variable number of causes are responsible for tinnitus and SHL. Moreover, ozonetherapy may interrupt the vicious circle due to a chronic oxidative stress and deranged muscle metabolism. Clearly the unbalanced NO/superoxide production contributes greatly to the diffused vascular damage and to a progressive involution of SCA. Song C. W., Lee I., Hasegawa T., Rhee J. G., Levitt S. H. Increase in pO. Bocci V., Travagli V., Zanardi I. Transitory improvements of mental or of sexual activities are not consistent findings and long-term treatments are often associated with adverse effects as irsutism, diabetes, and prostatic hypertrophy. By releasing endorphins (End. Moreover, at least two of the main enzymes degrading 4-HNE, namely GSH-S-transferase and aldehyde dehydrogenase have been found reduced in liver microsomes and mitochondria of diabetic rats (Traverso et al., 2002). Improper and excessive subcutaneous injection of gas is very dangerous! Can we combine the treatments? So I asked him: when did you last check your instrument? He said: I have never checked it! 5th week: 60 mcg/ml for a total ozone dose of 13.50mg per treatment. It is sad to think that, while every day in the world one billion people are starving, in the so-called developed countries a huge amount of money is being spent to delay skin ageing or mask small imperfections. On the basis of the experimental evidence in vitro provided by Chen et al. Chen Q., Espey M. G., Sun A. Y., et al. The rationale of the approach, a possible timing of application, either alone in patients with minimal residual disease or in combination with orthodox treatments and the already used therapeutic scheme have been described in details. A., Sheremata W. A., Blumhardt L. D., Rice G. P., Libonati M. A., Willmer-Hulme A. J., Dalton C. M., Miszkiel K. A., OConnor P. W. A controlled trial of natalizumab for relapsing multiple sclerosis. So, how does ozone act? Wasser G. H. Behandlung von Verletzungen mit ozoniertem Wasser. Rattan V., Shen Y., Sultana C., Kumar D., Kalra V. K. Diabetic RBC-induced oxidant stress leads to transendothelial migration of monocyte-like HL-60 cells. These processes are demonstrated by an increase of ROS and isoprostanes (Morrow et al., 1995; Morrow and Roberts, 1997; Basu, 2004), activation of NF-KB with increased synthesis of IL-1,TNF-, IL-4, IL-6, IL-8, and inactivation (by oxidative damage) of 1-antitrypsin and leukoproteinase inhibitors, unable to counteract elastase, cathepsins and matrix metalloproteinases and reduction of histone deacetylase-2 (HDAC2) secondary to increased oxidative and nitrative stress in the lungs (Smith et al., 1997; Barnes, 2000; Gross and Hunninghake, 2001; Kamp, 2003; Langen et al., 2003; Barnes, 2009a, b). Moreover no sign of toxicity, as evaluated by examining several biochemical parameters and even natural killer activity, has become apparent (Tylicki et al., 2003, 2004a; Biedunkiewicz et al., 2004). Procure a state of well-being in patients by activating the neuro-endocrine system. Oral simvastatin treatment in relapsing-remitting multiple sclerosis. In order to suppress asthma, further clinical research is required for the effective induction of Tregs. Today there is a cornucopia of reports linking inflammation (hence, chronic oxidative stress) due to renal diseases and haemodialysis (Knudsen et al., 1989; Ceballos-Picot et al., 1996b; Hasselwander and Young, 1998; Witko-Sarsat et al., 1998; Morena et al., 2000; Rousseau et al., 2000; Galli, 2007; Piroddi et al., 2007). Travagli, V., Zanardi, I., Bernini, P. et al., 2010, Effects of ozone blood treatment on the metabolite profile of human blood. Improving chelation therapy and a supplement of antioxidants (Asplund, 2002), can be useful but they are unable to abate the chronic oxidative stress. Kimberlin D. W., Rouse D. J. Haematological malignancies in children are dealt with remarkable success by orthodox medicine and conceptually I doubt that ozone therapy would be useful. I firmly believe that the IP route is interesting and, although it is not easily accessible, the IP dialysis methodology is fairly safe and available. Second of two parts. During the last three decades, the theory that hormonal decline may be an important cause of aging has gathered momentum, with the postulation that hormonal replacement may result in rejuvenating frail or ailing elderly people. ) that, by rapidly reacting with nitric oxide, on one side it decreases vascular relaxation (increases blood pressure and platelet aggregation!) While any AHT represents a small oxidative stress, this is quite transitory, calculated and promptly corrected by the antioxidant system. Liver histological results, whenever possible before and 3 months after the 6-month course. Owen C. G., Fletcher A. E., Donoghue M., Rudnicka A. R. How big is the burden of visual loss caused by age related macular degeneration in the United Kingdom? The next table reports tentative guidelines regarding ozone concentrations within the therapeutic window to be used in different pathologies with the classical ozonated AHT, twice weekly. I believe that in the 1970s, Dr. Alexander Balkanyi in Zurich has been the first to have the idea to inject small volumes of ozone in patients affected by tendinitis and myofascial pain. Herrmann M., Voll R. E., Kalden J. R. Etiopathogenesis of systemic lupus erythematosus. While I admit that experimental results in rats may not always be duplicated in patients, we must acknowledge the paradoxical power of ozone in rapidly inducing the defensive upregulation of antioxidant enzymes. I always tell them a true story: several years ago, after a lecture in which I had pointed out the serious problem of unreliability of ozone generators and their unavoidable decay, one famous ozonetherapist working in Milan looked very worried. If the proposed therapeutic combination will yield positive results, we will be able to spare later on the misery of many patients and the cost of haemodialysis. In the case of fibromyalgia, our statistics are very meagre compared to those reported by Loconte (2000) and Cosentino et al. Joyce J., Rabe-Hesketh S., Wessely S. Reviewing the reviews: the example of chronic fatigue syndrome. Since that time, great strides have been made in understanding the immunologic derangements occurring in psoriasis and two studies (reported in Section 9.5, Autoimmune diseases) have shown that administration of biological response modifiers, namely of two antibodies: the first against TNF-alpha (etanercept) and the second against a leukocyte-function-associated antigen1, LFA-1 (efalizumab) have yielded a remarkable improvement (albeit not definitive) in the majority of patients (Kupper, 2003). PARADOXICALLY, it can elicit beneficial effects. In either post-menopausal or ovariectomized women, small doses of estrogens may produce some benefits (improvement of memory and of the HDL/LDL ratio) but if taken daily may also cause serious drawbacks as breast and lung cancer and vascular disorders (Peterson, 1998; Chlebowski et al., 2009). In reality, it is an easy approach consisting in one or several (up to four) injections of 510ml of gas per site (Figs. However, Clark et al. At the Nephrology Unit of Siena Hospital, prof. N. Di Paolo and I also had the opportunity of carrying out ozone therapy, with the EBOO technique, in very critical patients, one of which was affected from necrotizing fasciitis (Fig. Successively Cuban Authors have repeatedly shown that it is possible to induce the adaptation and a state of resistance to oxidative stress by preconditioning rats with ozone (via rectal route) for several days BEFORE the noxious stimulus (Len et al., 1998; Peralta et al., 1999; 2000; Borrego et al., 2004). After a few years he also showed that polyunsaturated dietary fats could induce a high cancer rate in mice. Garber G. E., Cameron D. W., Hawley-Foss N., Greenway D., Shannon M. E. The use of ozone-treated blood in the therapy of HIV infection and immune disease: a pilot study of safety and efficacy. While certainly we are not overlooking the importance of antidiabetic drugs, statins, antihypertensive agents and so forth, we judge it deplorable to disregard the benefit of a combined ozonetherapy. B., Liew F. Y. Interleukin 15: a proinflammatory role in rheumatoid arthritis synovitis. The unbalanced equilibrium between reactive oxygen species and antioxidants, particularly a low reduced glutathione/oxidised glutathione ratio, usually precedes hypertension in diabetes. Kudravcev, B. P., Miroshin, S. J., and Semyonov, S. V., 1995, The use of ozonized solutions in complex treatment of peritonitis, in. Present D. H., Rutgeerts P., Targan S., Hanauer S. B., Mayer L., van Hogezand R. A., Podolsky D. K., Sands B. E., Braakman T., DeWoody K. L., Schaible T. F., van Deventer S. J. H. Infliximab for the treatment of fistulas in patients with Crohns disease. Another problem is that, in order to achieve striking results, enthusiastic clinicians tend to administer pharmacological doses of a single hormone, thus possibly disrupting the physiological equilibrium with unforeseeable consequences. While GSH-Rd utilizes the coenzyme NADPH to recycle GSSG to the original level of GSH, the oxidized NADP is reduced after the activation of the pentose phosphate pathway, of which G6PD is the key enzyme. However, this aspect has not been evaluated. Semenza G. L. Hypoxia-inducible factor 1: oxygen homeostasis and disease pathophysiology. In: Ceccherelli F., Giron F., editors. Obviously this simple solution must be based on the feasibility of achieving a small ozonation of blood without any release of toxic materials from the filter (Travagli et al., 2010a). Bocchi, L., Cervelli, C., and Ferrata, P., 2000, Lossigeno-ozono terapia nel trattamento delle patologie vertebrali lombari, in. Not to be forgotten that in SCA, sickle erythrocytes are already generating great amounts of ROS and LOPs. Thus, more than the mechanical compression as primum movens, it is the ischemia of the arterial afferents, possibly associated with venous stasis and inflammatory reaction that sustains chronic pain by releasing PLA2, several proteinases and cytokines. Heaney M. L., Gardner J. R., Karasavvas N., et al. Interestingly, epidural injections of the anti-inflammatory methylprednisolone transitorily improve leg pain and sensory deficits in patients with sciatica due to a herniated disc (Carette et al., 1997). I have often said that ozonetherapy is vexed by several problems: the serious control and maintenance of generators is a crucial one and, only recently, after several warnings, some ozonetherapists have become aware of this. Alternatively, on the basis of the minimal ozone dose, we can entertain the simple and inexpensive solution of using the same dialysis filter, simply substituting the dialysate with the gas mixture (oxygen 99.5% ozone 0.5%) in the space external to the hollow fibres, where the blood is circulating, for the final 10min of ozonation. Dale J. J., Ruckley C. V., Harper D. R., Gibson B., Nelson E. A., Prescott R. J. Randomised, double blind placebo controlled trial of pentoxifylline in the treatment of venous leg ulcers. Immunosuppressive therapy. Wahl C., Liptay S., Adler G., Schmid R. M. Sulfasalazine: a potent and specific inhibitor of nuclear factor kappa B. Warlow C., Sudlow C., Dennis M., Wardlaw J., Sandercock P. Stroke. My original idea was to use in peritoneal carcinosis in ovarian cancer (and even in pleural mesothelioma) because ozone could exceptionally express a direct cytotoxic action as well as an immunomodulatory activity both by stimulating resident macrophages and the immune system after absorption of ozone messengers via the vast lymphatic system. The schedule of two treatments per week appears valid and well accepted by patients but, while we should start with a 225ml volume of blood and an ozone concentration of 20 mcg/ml, during a 4 week period, we should escalate the ozone concentration up to 5060 mcg/ml. However, in pathological circumstances such as chronic hepatitis, ischemia-reperfusion and severe haemoglobinopathies, the liver, that is the main repository of xantine dehydrogenase (XDH) allows its conversion to xantine oxidase (XO) and to its release in the circulation (Parks and Granger, 1983; Tan et al., 1993; Sarnesto et al., 1996; Houston et al., 1999). Careful preservation of vascular accesses is a matter of life or death but either AHT, or the glucose or saline-peroxide infusion, or EBOO are not adding a superfluous stress. Baulieu E.-E., Robel P. Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) as neuroactive neurosteroids. These supergifted erythrocytes, as we called them, due to a higher content of 2,3-DPG and antioxidant enzymes, during their life-time, become able to deliver more oxygen into ischemic tissues (Bocci, 2002; Rokitansky et al., 1981; Mattassi et al., 1987; Romero Valdes et al., 1993; Tylicki et al., 2001, 2003, 2004; Giunta et al., 2001; Clavo et al., 2003). Sinclair D. A. McCord J. M. Free radicals and inflammation: protection of synovial fluid by superoxide dismutase. (Mattox and Simmons, 1977). B., Durham S. R. Activation of CD4+ T cells, increased TH2-type cytokine mRNA expression, and eosinophil recruitment in bronchoalveolar lavage after allergen inhalation challenge in patients with atopic asthma. It has been thought to solve this problem by using either creams or slow-release patches, which may be better than oral administration or injection. In spite of the fact that more than 4,000 papers have been published on CFS (Joyce et al., 1998), its aetiology and pathophysiology remain ambiguous, but it cannot be excluded that CFS is first triggered by an undefined viral or bacterial infection able to induce a chronic infection with a concomitant immunological dysregulation (Caligiuri et al., 1987; Landay et al., 1991; Konstatinov et al., 1996; Komaroff and Buchwald., 1998). Previous suggestions using sodium hypochlorite do not appear as effective as ozone (Inaba et al., 1996; Dogan and Qalt, 2001), According to Lynchs group, some 80% of PRCLs can be successfully treated by the quick, simple, inexpensive and painless use of ozone on root dentine carious lesions as an alternative to the conventional and painful drilling and filling management of PRCLs. Steuer-Vogt M. K., Bonkowsky V., Ambrosch P., Scholz M., Neiss A., Strutz J., Hennig M., Lenarz T., Arnold W. The effect of an adjuvant mistletoe treatment programme in resected head and neck cancer patients: a randomised controlled clinical trial. Wessely S. Chronic fatigue: symptom and syndrome. Bressler N. M., Bressler S. B., Fine S. L. Age-related macular degeneration. The results of a number of studies vary somewhat (Cinnella and Brayda-Bruno, 2001), but they can be summarized as: about 40% optimal, 3540% marked improvement, 1525% minimal or no result. Knoch H.-G., Roschke W., Klug W. Ozone/oxygen therapy in proctology. Stocco D. M., McPhaul M. Physiology of testicular steroidogenesis. A multicenter, randomized, double-blind, placebo-controlled study of immune modulation therapyin patients with symptomatic peripheral arterial diseases: the SIMPADICO trial. This line of research is exciting but Frei and Lawson (2008) have correctly emphasized the need of carrying out a precise analysis of the mechanisms of action. Both approaches have not improved the symptoms either during or after the suspension of therapy. In: Beck E. G., Viebahn-Hnsler R., editors. Vasodilatation by increased release of nitric oxide or and prostacyclin. B., Peroni O. D., Fryer L. G., Muller C., Carling D., Kahn B. Our calculated therapeutic stress on bloodex vivomust be clearly distinguished from the life-long, endogenous, oxidative stress due to the ordinary oxygen breathing because, although it seems a paradox, ozonetherapy can upregulate the antioxidant defenses. The treatment is interpreted as a therapeutic shock occurring ex vivo during the exposure of blood to ozone and transmitted into the donor during blood reinfusion. Clinical results so far available have been objectively discussed showing that ozonetherapy is often more useful than orthodox treatments in a FIRST category of diseases such as: For these pathologies ozone is a real wonder drug. Aslan M., Ryan T. M., Adler B., Townes T. M., Parks D. A., Thompson J. This is very unsatisfactory, mostly because, in spite of a small progress, the death rate remains high and resolutive breakthroughs are not yet in sight.
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