O3 Ozone - Oxygen Medicine:

100% Virus Inactivation - HIV, Herpes, Hepatitis in Blood

Are worry-fee transfusions just a whiff of ozone away?

Ref: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1490857/pdf/cmaj00308-0061.pdf

Ref: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1490857/

Video: http://www.youtube.com/user/ozoneresearch

Video: http://www.ozonehospital.com/

Video: International Ozone Research, Information & Interviews - Canadian Government Scientists, Canadian Department of Nation Defence, U.K. Doctors & German Ozone Doctors

Are worry-fee transfusions just a whiff of ozone away?

Scientists in Canada and the United States are investigating the use of ozone to destroy the human immunodeficiency virus (HIV), the hepatitis and herpes viruses and other infectious agents in the blood used for transfusion.

The studies were endorsed by medical circles of the North Atlantic Treaty Organization (NATO) because of a concern that viral pandemics have compromised the ability of world blood banks to meet urgent and heavy military demands.

NATO's fears are justified...

The World Health Organization recently estimated that more than 200 million people are long-term carriers of hepatitis B virus and that about 13 million people are now infected with known HIV strains."2 The spread of HIV (and thus the threat to blood banks and military organizations) is being impelled by socioeconomic factors and the worldwide recession.

In Southeast Asia, for example, a substantial increase in the number of reported cases of acquired immunodeficiency syndrome (AIDS) has been directly attributed to the sale of prepubescent Burmese girls to prostitution lords and madams in Thailand.

The children, who are obliged to service up to 15 customers daily (British Broadcasting Corporation World Service News, November 1992), are sold by their parents to pay for food and to finance drug addiction. An epidemic of AIDS in the Thai military population seems to be associated with prostitution in the country.

As HIV spreads among heterosexual men and women3 a concomitant increase in the worldwide rejection rate of donors and blood, which now reaches 20% to 30%, must be expected.'

Laboratories in Canada, the United States and other Countries have preliminary evidence that sterilization with ozone is feasible:

Canada - 1993:

In a brief to the NATO Blood Committee' the surgeon general of the Canadian Armed Forces reported on joint U.S. Canadian findings that within the sensitivity of the screening methods used, a 3-minute ozonation of serum spiked with one million HIV-1 particles per millilitre would achieve virtually 100% viral inactivation (loss of infectivity).

Ref: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1490857/

It was also found that the procedure would destroy several other lipid-encapsulated viruses, including simian immunodeficiency virus and various strains of interest to veterinarians:

Bacteria - Aeromonas Hydrophila - Coliform Bacteria - Staphylococcus aureus

Coxsackievirus

Echovirus

Fungi - Candida Utilis

Hepatitis Viruses

Herpes Viridae - Simplex, Varicella-Zoster, Cytomegalovirus, Epstein-Barr Virus.

Lipid-Encapsilated Viruses

Orthomyxoviridae - Influenza

Paramyxoviridae - Mumps, Measles

Retroviridae - Human Immunodeficiency- Virus (HIV), Simian Immunodeficiency Virus, Anemia Virus, Equine Infectious Virus

Rhabdoviridae - Rabies

Polioviridae

Germany - 195O's:

More than 10 000 units of human blood containing hepatitis virus were rendered safe
through treatment with a mixture of ozone (O3) and oxygen (O2) for transfusion."

Ref: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1490857/

Canadian interest in the technique evolved partly from the early German successes but mainly from in-vitro studies with ozone by Captain Michael E. Defence, in collaboration with virologist Dr. Michael O' Shaughnessy, at the Laboratory and Research Services Bureau, Laboratory Centre for Disease Control Ottawa.

Their experiments led to a pilot study patients with AIDS at the Ottawa General Hospital (approved by the Health Protection Branch and the hospital's ethics committee).4 The Canadian experiments with HIV and other viruses used gas-exchange technology from Mueller Medical International Inc. (Oakville, Ont.), with help from Medizone International Inc., New York.

Generated from oxygen by high-voltage or ultraviolet light, ozone can be delivered through a gas exchange cartridge or other system of media diffusion, at controlled concentrations, to infected culture media, blood and Factor VIII or other blood products.

If gas sterilization can be shown to meet Red Cross standards the technique could augment existing methods - micropore filtration, centrifugation and washing.5

Experimental Results

Two teams of US virologists have used comparable gas-diffusion techniques to confirm the Canadian findings, with the following results.

* HIV- 1 at concentrations of 1013 virions/L was inactivated in cell-culture media, plasma and purified Factor VIII preparations through ozonation (1200 ppm of ozone for 2 hours) by means of a hollow-fibre gas delivery system, with a minimal loss (10%) of the biologic activity of clotting factors.6

* Preliminary assessment of erythrocyte function and life span revealed no impairment. (Michael E. Shannon, Department of National Defence: personal communication, 1992).

* The presence of cells in the ozonized media did not prevent the inactivation of extracellular virions.'

* Ozonized biologic fluids, in which there is a presumed abundance of superoxide, singlet oxygen, hydroxyl and peroxyl radicals and other highly reactive species, had both extracellular and intracellular virucidal properties.7

* Because of a defective glutathione peroxidase system, HIV-infected lymphocytes readily lysed after ozonation and released presumably noninfective viral particles into the extracellular medium (Michael E. Shannon: personal communication, 1992).8

* Other infected cells maintained in pre-ozonized media exhibited a 40% reduction in the expression of HIV-1 core antigen (p24 protein).7

Mechanisms of Ozone Action

Ozone has long been used to destroy bacteria in municipal water supplies. Its destructiveness is partly attributed to the oxidation of unsaturated bonds oxidation generates hydroperoxides, which are transformed to peroxyl and hydroxyl radicals and to other reactive species, including aldehydes.

Peroxyl radicals attack proteins, and hydroxyl radicals induce disruptive structural changes in cell membranes.910 Virus-infected cells are considered less able to withstand such oxidative influences than uninfected cells, which have intact antioxidant mechanisms.

Thus, at the relatively low ozone concentrations required to sterilize whole blood, even intracellular infective agents can likely be destroyed selectively without uninfected tissue being substantially altered.

Several other specific mechanisms have been postulated for the destruction of retroviruses, including HIV, by reactive oxygen intermediates: inactivation of viral reverse transcriptase, which would otherwise transcribe the viral RNA genome into host cofactor of the transcriptase; and interference with the ability of the HIV envelope glycoprotein gp 120 mutation of the genes10'1 may contribute to inactivation, especially of extracellular viruses, whose genes are unprotected by the cellular endonucleases and ligases that maintain DNA integrity.

Primate Studies

As compelling as this research may be, the efficacy and safety of blood sterilization with ozone remains to be proven. To this end, critical studies that make use of an isolate of a now fully characterized simian immunodeficiency virus have been initiated. These have involved extensive in-vitro research to clarify the optimal dose of ozone required for viral destruction in transfusion products.

Before extensive human trials can be considered it will benecessary to perform dose-response and toxicologic studies in animals to confirm the European evidence that systemic ozone therapy is safe (Michael E. Shannon: personal communication, 1992).

The experiments - a collaborative effort between scientists at the Department of National Health and Welfare, the Department of National Defence, the CanadianAnimal Disease Research Institute and Cornell University, Ithaca, NY - will address the fundamental question:

"Will whole blood or specific blood fractions highly virulent strain of simian immunodeficiency virus produce immunodeficiency disease in primates if the blood is treated with ozone before reinoculation?"

Discussion

Military physicians ruefully accept that during war and catastrophe-relief missions, especially in remote regions, urgently needed blood and blood products must be obtained from all available sources and that screening for infectious agents will not always be possible.

Although serologic tests for antibodies to HIV and viral proteins and nucleic acid have increased the safety of blood transfusions they do have limitations,'2-'4 particularly in the detection of unknown immunodeficiency factors.'5 Clearly, there is a concern that transfusions and transplants are not "HIV proof."'6"7

In 1991 AIDS was diagnosed in 747 transfusion recipients and 347 patients with hemophilia in the United States;18 there were an estimated 7200 such infections in 1984, before screening for HIV became routine.'9

In Canada, 279 of the 6560 patients with AIDS reported since 1979 were apparently infected through blood or blood products (Federal Centre for AIDS, Department of National Health and Welfare, Ottawa: personal communication, 1992).

Given the concerns of the military, the medical profession and the public there seems to be some urgency to the search for a rapid, reliable, portable and cost-effective method of blood decontamination that can destroy all known pathogens while preserving the functions of erythrocytes, platelets, coagulation factors and immune globulins.

Various decontamination procedures and agents - gamma irradiation and the use of direct heat (60°C) and steam, solvents and oxidizers (ether, alcohol, aldehyde and surfactants), antibodies and enzymes - have been shown to be partially effective, but they have major disadvantages: unsatisfactory sterilization, damage to erythrocytes (especially from aldehydes) and the risk of mutagenic and potentially carcinogenic contaminants being created.

Published and unpublished laboratory evidence attesting to the effectiveness of ozone against intracellular and extracellular HIV in whole blood, plasma and Factor VIII products indicates that ozonation, augmented by the filtration of leukocytes, may meet at least some of the essential requirements for decontamination.

However, the litmus tests will be studies of infectivity risk in primates and the screening of HIV-spiked blood, after ozonation, by means of the sensitive polymerase chain reaction (which amplifies minute quantities of viral nucleic acid to detectable levels2'-23); the results of these investigations will appraised with interest by blood bank facilities in both Canada and the United States.

Caution is required in the treatment of human disease with ozone because of the potential toxic effects of reactive oxygen intermediates, which are known to mediate damage to tissue. Indeed, several mechanisms of carcinogenesis associated with oxygen radicals have been defined,'0"'24 even though ozone has been found to inhibit cancer cells in vitro.25

Europe 1993:

A review of 300 000 patients who had been given more than 5 million ozone (O3) treatments concluded that when strict protocols were followed the rate of adverse effects was 0.6% ...
and that there was no evidence of carcinogenicity.

Ref: Jacobs MTH: Untersuchung uber Zwischenfalle und Typische Komplikationen in der Ozone-Sauerstoff Therapie (AufzugAPRIL 1, 1993 CAN MED ASSOC J 1993; 148 (7) 1159 auf der Dissertation). Ozo Nachrichten 1986; 1: 5

Canada 1990's:

A recent Canadian clinical trial of O3 Ozone in the treatment of AIDS patients
(by means of phlebotomy, ozonation of the blood sample and intramuscular reinoculation) showed no evidence of serious side effects.

Although vascular endothelial cells are susceptible to attack by oxygen radicals several biochemical species provide some protection. Vitamin C, uric acid, N-acetyl-L-cysteine and glutathione are known to scavenge oxygen radicals in the aqueous region o fcell membranes, but these water-soluble antioxidants are ineffective against peroxyl radicals in the lipid region, where vitamin E exhibits rather limited antioxidant efficiency.27 Additional defence against superoxide is provided by dismutase enzymes and against hydrogen peroxide by catalases and peroxidases.

In elderly people, those with HIV infection and possibly those with certain other viral infections these antioxidant and enzymatic mechanisms may be less efficient than in young, healthy people, so that peroxidative damage to endothelial cells becomes more probable. Extracellular oxidant injury seems to induce anticlotting mechanisms.28

Furthermore, the treatment of occlusive vascular disease with ozonized blood appears to stimulate the enzymatic conversion of L-arginine to citrulline, nitrite and nitrate by phagocytic cells. Small amounts of nitric oxide, a platelet disaggregator and vasodilator, in this pathway. The production of ozone.29,30

Thus, the various actions of endogenous and ozone-generated oxygen radicals have mixed clinical implications: the prevention of thrombus formation damage to the vascular lumen, obstruction of reparative hemostasis and extravasation are potential complications of therapy when ozone concentrations exceed 50,ug/mL (which may be necessary to destroy retroviruses effectively).

The adverse effects of endogenous reactive oxygen intermediates probably vary with age, diet and physiologic state.3' Oxygen-radical damage has been related disease of the central nervous and cardiovascular systems, including hypertension, damage to blood vessels in the brain and cerebral ischemia.3233

Radicals may also oxidize catecholamines and mediate processes may be associated with dementia, demyelination and other degenerative neurologic disorders, possibly other infectious agents such as papovavirus and cytomegalovirus35), which evokes an immune-driven accumulation of oxidants. If these adverse reactions complicate future clinical trials it may be possible to counteract them with the use of covalently modified or lipid encapsulated antioxidants and protective enzymes with prolonged circulatory half-lives.36"37

Oxygen radicals present something of a paradox in biology: the accumulation of endogenous or xenogenous species is exceedingly harmful to tissues; yet from a defensive perspective radicals may be highly functional.

In its response to malignant cells and infectious agents the repertoire of the immune system usually includes the generation of reactive oxygen intermediates.

Thus, macrophages reduce oxygen to superoxide as they attempt to eliminate tumours,38 and various phagocytic cells produce superoxide, hydrogen peroxide and hydroxyl when killing bacteria39 and in responding to irritant chemicals or inorganic particles.40

Similarly, the generation of hydroxyl by natural killer cells seems to be critical to their cytotoxic capability.4' Oxygen radicals are also thought to function in the early events leading to the activation and proliferation of T lymphocytes.42

It appears that HIV infection intensifies these normal immunologic oxidative mechanisms to a destructive scale. A state of chronic oxidative stress can be induced in vitro in lymphocyte (T4) subpopulations by inflammatory cytokines (interleukins 1 and 6 and tumour necrosis factor-a), which stimulate mass production of reactive oxygen intermediates in infected cells.

Glutathione peroxidase (a cellular antioxidant) is rapidly depleted by these accumulating intermediates. The virus-laden cells lose their ability to detoxify amassing radicals and xenobiotics.8 This oxidative stress may macrophages and other infected cell lines (e.g., in the skin, intestines, central nervous system and spleen).

This evidence is critical to the strategy behind the use of ozone for decontaminating blood. Since cells infected with HIV-1 are less able than healthy cells to cope with oxidative stress they quickly lyse in the presence of ozone, and their viral contents are exposed to oxidative disinfection.

Similarly, extracellular retrovirus may be fully deactivated by direct oxidative assault on the viral capsule and RNA. There are other complicating factors: respiratory syncytial virus infection is partly mediated by the superoxide produced by neutrophils;43 reactive oxygen intermediates cause extensive damage to pulmo- nary tissue as well as bronchial hyperresponsiveness (including bronchoconstriction);44 and evidence of oxygen radical involvement can often be found in plasma as lipid peroxidation products.45

Such evidence supports the idea that superabundant immune-generated oxygen radicals may be culprits or accomplices in many of the cytopathologic features observed in AIDS, such as the fusion of infected multinucleated giants that produce HIV particles in abundance,46 impaired T-lymphocyte proliferation, altered differentiation of T and B cells and impaired activity of natural killer lines.8

Perhaps the firmest indictment of oxygen radicals and hydrogen peroxide as mediators of HIV infection has come recently from the Ludwig-Maximilians University, in Munich, where molecular biologists have suggested that the expression and replication of nine or more HIV-1 genes in human T lymphocytes results from the oxidation of cytoplasmic initiators. These "activated" proteins bind to initiation sites on the viral genome.8,47,48

The possibility that oxygen radicals and peroxides generated by ozone might contribute to oxidative stress and thereby potentiate HIV transcription and translation in dormant (i.e., provirus +) T cells is a clinical concern.

Inflammatory cytokine responses were not evaluated in the Canadian clinical studies, but the individual p24 viral antigen profiles of patients were unaffected by low doses of ozone. This suggests that the treatment did not increase (or decrease) HIV transcription (Michael E. Shannon: personal communication, 1992).4

A further concern contemplated by Canadian scientists is that ultraviolet light, which is used to irradiate ozonized blood in one technology now under evaluation, has been found to activate both laboratory-hybridized and latent HIV genes in cultured human cells.49

However, an absorption spectrum for solar radiation50 indicates that at atmospheric (normal ozone layer) concentrations oxygen ozone may completely absorb ultraviolet light at 253.7 nm (the energy fluence being considered for blood decontamination).

The simultaneous perfusion of blood with ozone may therefore prevent the activation of integrated HIV genes by ultraviolet energy.49 Treating blood with a combination of ultraviolet light and ozone does not appear to initiate spontaneous cell division among lymphocytes and monocytes (Dr. Anthony Bolton, consultant to Intermune Life Sciences Inc., Etobicoke, Ont.: personal communication, 1992).

This suggests that the potently virucidal combination of ultraviolet energy and ozone in blood decontamination devices is unlikely to switch on viral genes. (The HIV-activation issue has also been enlivened by findings that other viruses [vaccinia virus and herpesvirus-615" 52 and tumour necrosis factor-a53 can stimulate HIV expression.)

The systemic use of ozone in the treatment of AIDS could not only reduce the virus load but also possibly revitalize the immune system. Although ozone therapy may seem rather novel, the concept of oxygen radicals being used to destroy viruses in biologic fluids and in cells is not entirely foreign to pharmacology: it is believed, for example, that some antimalarial drugs eliminate Plasmodium by inducing intraerythrocytic oxidative stress.54

With regard to the effect of ozone Italian studies have suggested that ozone enhances the production of interleukin-2 (the T-lymphocyte antiviral immune peptide, interferon-y.55 There is (recombinant) sisterpeptide, interferon-a, can inhibit the expression by infected cells of p24 viral core protein.56 Interferonstimulated macrophages may generate less superoxide and hydrogen peroxide in response to HIV proliferation and lymphokine production may be restrained.57

Conclusion

The potency of biologic oxidizing agents is well known and may be easily and vividly demonstrated by the classic microbiologic test in which a few drops of 3% hydrogen peroxide solution are added to anagar culture of Staphylococcus aureus (catalase-positive).

Findings at laboratories in North America and Europe have demonstrated that ozone has remarkable potency against disease factors in blood products.

However, the importance of animal studies in evaluating the efficacy and safety of ozone in blood decontamination and perhaps, eventually, in treating human immunodeficiency is clear. Blood approved for transfusion on the basis that it has undergone ozone sterilization, alone or in combination with another method, should ideally carry a risk of infection at least as low as that of the blood that passes the most rigorous screening methods now in use, and it should not cause viral or other disease or immune complications.

Thus, to determine toxicologic indices is a necessary step toward finding the optimum therapeutic range. Concentrations of ozone exceeding 100 ,ug/mL, which are noxious to cells in vitro,55 may be required to overcome the effects of circulating antioxidants27 and HIV-shielding blood proteins.6 Preliminary findings suggest, however, that less than a fifth of this concentration may be effective (Michael E. personal communication, 1992).

References

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3. Anderson RM, May RM: Understanding the AIDS pandemic. Sci Am 1992; 266 (5): 58-66

4. Garber GE, Cameron DW, Hawley-Foss N et al: The use of ozone-treated blood in the therapy of HIV infection and immune disease - a pilot study of safety and efficacy. AIDS 1991; 5: 981-984

5. Clinical Guide to Transfusion: Products & Practices, Canadian Red Cross Society, Ottawa, 1987

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7. Carpendale MTF, Freeberg JK: Ozone inactivates HIV at noncytotoxic concentrations. Antiviral Res 1991; 16: 281-292

8. Staal FJT, Ela SW, Roederer M et al: Glutathione deficiency and human immunodeficiency virus infection. Lancet 1992; 339: 909-912

9. Bland J: Biochemical consequences of lipid peroxidation. J Chem Ed 1978; 55: 151

10. Sahu SC: Role of oxygen free radicals in the molecular mechanisms of carcinogenesis: a review. J Environ Sci Health 1991; C9 (1): 83-112

11. McBride TJ, Preston BD, Loeb LA: Mutagenic spectrum resulting from DNA damage by oxygen radicals. Biochemistry 1991; 30: 207-213

12. Surgenor DM, Wallace EL, Hao SHS et al: Collection and transfusion of blood in the United States, 1982-1988. N Engl JMed 1990; 322: 1646-1651

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21. Mullis KB: The unusual origin of the polymerase chain reaction. Sci Am 1990; 262 (4): 56-61, 64-65

22. Persing DH: Polymerase chain reaction: trenches to benches. J Clin Microbiol 1991; 29: 1281-1285

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24. Sweet F, Kao MS, Lee SCD: Ozone selectively inhibits growth of human cancer cells. Science 1 980; 209: 931 -933

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26. Niki E: Lipid antioxidants: how they may act in biological systems. Br J Cancer Suppl 1987; 8: 153-157

27. Shatos MA, Doherty JM, Orfeo T et al: Modulation of thefibrinolytic response of cultured human vascular endothelium by extracellularly generated oxygen radicals. J Biol Chem 1992; 267: 597-601

28. Marletta MA, Yoon PS, Iyengar R et al: Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate. Biochemistry 1988; 27: 8706-8711

29. Bolton A: Report on Scientific Studies to Elucidate"O-on-O-Med" Treatment of Peripheral I ascular Disease, Intermune Life Sciences, Etobicoke, Ont, 1992

30. Halliwell B, Gutteridge JMC: Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem J 1984; 219 (1): 1-14

31. Giunta S, Galeazzi L, Groppa G: Oxygen toxicity induced by isoproterenol oxidation on living cells. An in vitro prokaryotic model. Arch Gerontol Geriatr 1990; 10: 207-216

32. Rubanyi GM: Vascular effects of oxygen-derived free radicals. Free Radic Biol Med 1988; 4: 107-120

33. Halliwell B, Cutteridge JMC: Oxygen radicals and the nervous system. Trends Neurosci 1985; 8 (1): 22-26

34. Carne CA: Neurological manifestations. In Adler MW (ed): ABC ofAIDS, 2nd ed, BMJ, London, 1991: 30-32

35. Turrens JF: The potential of antioxidant enzymes as pharmacological agents in vivo. Xenobiotica 1991: 21: 1033-1040

36. LeBel CP, Bondy SC: Oxygen radicals - common mediatorsof neurotoxicity. Neurotoxicol Teratol 1991; 13: 341-346

37. Hancock JT, White JI, Jones OTG et al: The use ofdiphenylene iodonium and its analogues to investigate the role of the NADPH oxidase in the tumoricidal activity of macrophages in vitro. Free Radic Biol Med 199 1; 1 1: 25-29

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39. Phillips BJ, Anderson D, Gangolli SD: Influence of phagocyte-derived active oxygen species in tissue responses to tumour promoters and irritants. Food Chem Toxicol 1986; 24: 681-683

40. Suthanthiran M, Solomon SD, Williams PS et al: Hydroxyl radical scavengers inhibit human natural killer cell activity.Nature 1984; 307: 276-278

41. Chaudhri G, Hunt NH, Clark IA et al: Antioxidants inhibit proliferation and cell surface expression of receptors for interleukin-2 and transferrin in T lymphocytes stimulated with phorbol myristate acetate and ionomycin. Cell Immunol 1988; 115: 204-213

42. Faden H, Kaul TN, Ogra PL: Activation of oxidative and arachidonic acid metabolism in neutrophils by respiratorysyncytial virus antibody complexes: possible role in disease. J Infect Dis 1983; 148: 110-116

43. Doelman CJA, Bast A: Oxygen radicals in lung pathology. Free Radic Biol Med 1990; 9: 381-400

44. Ward PA, Till GO, Hatherill JR et al: Systemic complement activation, lung injury, and products of lipid peroxidation. J Clin Iniest 1985; 76: 517-527

45. Lifson JD, Reyes GR, McGrath MS et al: AIDS retrovirusinduced cytopathology: giant cell formation and involvementof CD4 antigen. Science 1986; 232: 1123-1126

46. Schreck R, Rieber P, Baeuerle PA: Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappa B transcription factor and HIV-1. Eur Mol Biol Org J 1991; 10: 2247-2258

47. Haseltine WA, Wong-Staal F: The molecular biology of the AIDS virus. Sci Am 1988; 259 (4): 52-62

48. Wallace BM, Lasker JS: Awakenings . UV light and HIV gene activation. Science 1992; 257: 1211-1212

49. Goody RM: Atmospheric Radiation: I. Theoretical Basis, Clarendon Pr, Oxford, 1964

50. Stellrecht KA, Sperberk K, Pogo BCT: Activation of the human immunodeficiency virus type I long terminal repeat by vaccinia virus. J Virol 1992; 66: 2051-2056

51. Ensoli B, Lusso P, Schacter F et al: Human herpes virus-6 increases HIV-1 expression in coinfected T cells via nuclear factors binding to the HIV-1 enhancer. Eur Mol Biol Org J 1989; 8: 3019-3027

52. Archer DL: Food counselling should be given to all persons infected with the human immunodeficiency virus. J Infect Dis 1990; 161: 358-359

53. Clark IA, Hunt NH: Evidence for reactive oxygen intermediates causing hemolysis and parasite death in malaria. Infect Immun 1983; 39 (1): 1-6

54. Bocci V, Paulesu L: Studies on the biological effects of ozone: induction of interferon-gamma on human leucocytes. Haematologica 1990; 75: 510-515

55. McDonald JA, Caruso L, Karayiannis P et al: Diminished responsiveness of male homosexual chronic hepatitis-B virus carriers with HTLV-III antibodies to recombinant alphainterferon. Hepatology 1987; 7: 719-723

56. Oppenheim JJ, Ruscetti FW, Steeg P: Interleukins and interferons. In Stites DP, Stobo JD, Fudenberg HH et al (eds): Basic and Clinical Immunology, 5th ed, Lange, Los Altos, Calif. 1984: 86-103

by A C Braggs - Medical Science News - Information Scientific Medicale

Journal List > CMAJ > v.148(7); Apr 1, 1993, CMAJ. 1993 April 1; 148(7): 1155–1160.

Ref: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1490857/

Full Article: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1490857/pdf/cmaj00308-0061.pdf

Video - International Ozone Research, Information & Interviews - Canadian Government Scientists, Canadian Department of Nation Defence, U.K. Doctors & German Ozone Doctors