Mittwoch, 31. Juli 2013

Wissenschaftliche Arbeiten von Dr. Thomas Hesselink

Oxides Of Chlorine As Therapeutic Agents

By Thomas L. Hesselink, MD of Aurora, Illinois

1st Edition - Copyright 2007 - All rights are reserved.
This communication may not be reproduced in whole or in part
without written permission from the author.

DISCLAIMERS:


  • The information presented within these articles and accompanying communications is offered for legitimate educational and research purposes only.
  • This exists as an exercise of the author's constitutional rights to freedom of speech and to freedom of the press.
  • Nothing herein may be construed as providing:
    medical advice, manufacturing advice, business advice, nor any advice whatsoever, nor endorsement of any kind.
  • No claims, no guarantees nor promises of suitability or efficacy for any purpose are made.
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~~~ Links To Articles ~~~

On The Mechanisms Of Toxicity Of Chlorine Oxides
Against Malarial Parasites - An Overview
Research Protocols And Precautions:
WWW References Pertaining To Oxides Of Chlorine:

Bibliography Of Biologic And Therapeutic Oxidation

Dictionary Of Bio-Oxidative Medicine

Lectures In Hypertext - Home / Start Page


On The Mechanisms Of Toxicity Of Chlorine Oxides
Against Malarial Parasites - An Overview

By Thomas Lee Hesselink, MD
Copyright September 6, 2007

  • The purpose of this article is to propose research.
  • Nothing in this article is intended as medical advice.
  • No claims, promises nor guarantees are made.

ABSTRACT

Sodium chlorite (NaClO2) sodium chlorite can be acidified as a convenient method to produce chlorine dioxide (ClO2) chlorine dioxide which is a strong oxidant and a potent disinfectant. A protocol has been developed whereby a solution of these compounds can be taken orally. This procedure rapidly eliminates malaria and other infectious agents in only one dose. Chlorine dioxide (ClO2) is highly reactive with thiols (RSH) a generalized thiol , polyamines spermidine 
an example of an important polyamine , purines adenine 
an example of an important purine , certain amino acids and iron, all of which are necessary for the growth and survival of pathogenic microbes. Properly dosed this new treatment is tolerable orally with only transient side effects. More research to better document efficacy in malaria and in other infections is urgently called for.

DISCOVERY

Jim Humble, a modern gold prospecting geologist, needed to travel to malaria infested areas numerous times. He or his coworkers would on occassion contract malaria. At times access to modern medical treatment was absolutely unavailable. Under such dire circumstances it was found that a solution useful to sanitize drinking water was also effective to treat malaria if diluted and taken orally. Despite no formal medical training Mr. Humble had the innate wisdom to experiment with various dosage and administration techniques. Out of such necessity was invented an easy to use treatment for malaria which was found rapidly effective in almost all cases.

The procedure as used by Mr. Humble follows: A 28% stock solution of 80% (technical grade) sodium chlorite (NaClO2) sodium chlorite is prepared. The remaining 20% is a mixture of the usual excipients necessary in the manufacture and stabilization of sodium chlorite (NaClO2) powder or flake. Such are mostly sodium chloride (NaCl) ~19% sodium chloride , sodium hydroxide (NaOH) <1% sodium hydroxide , and sodium chlorate (NaClO3) <1% sodium chlorate . The actual sodium chlorite (NaClO2) present is therefore 22.4%. Using a medium caliber dropper (25 drops per cc), the usual administered dose per treatment is 6 to 15 drops. In terms of milligrams of sodium chlorite (NaClO2), this calculates out to 9mg per drop or 54mg to 135mg per treatment. Effectiveness is enhanced, if prior to administration the selected drops are premixed with 2.5 to 5 cc of table vinegar acetic acid or lime juice or 5-10% citric acid citric acid and allowed to react for 3 minutes. The resultant solution is always mixed into a glass of water or apple juice and taken orally. The carboxylic acids neutralize the sodium hydroxide (NaOH) sodium hydroxide and at the same time convert a small portion of the chlorite (ClO2-) sodium chlorite to its conjugate acid known as chlorous acid (HClO2) chlorous acid . Under such conditions the chlorous acid (HClO2) will oxidize other chlorite anions (ClO2-) sodium chlorite and gradually produce chlorine dioxide (ClO2). chlorine dioxide Chlorine dioxide (ClO2) appears in solution as a yellow tint which smells exactly like elemental chlorine (Cl2) chlorine . The above described procedure can be repeated a few hours later if necessary. Considerably lower dosing should be applied in children or in emaciated individuals scaled down according to size or weight. The diluted solution can be taken without food to enhance effectiveness but this often causes nausea. Drinking extra water usually relieves this. Nausea is less likely to occur if food is present in the stomach. Starchy food is preferable to protein as protein quenches chlorine dioxide (ClO2) chlorine dioxide . Significant amounts of vitamin C (ascorbic acid) ascorbic acid must not be present at any point in the mixtures or else this will quench the chlorine dioxide (ClO2) chlorine dioxide and render it ineffective. For the same reason antioxidant supplements should not be taken on the day of treatment. Other side effects reported are transient vomiting, diarrhea, headache, dizziness, lethargy or malaise.

EXPLORING BENEFITS

I first learned of Jim Humble's remarkable discovery in the fall of 2006. That sodium chlorite (NaClO2) or chlorine dioxide (ClO2) could kill parasites in vivo seemed immediately reasonable to me at the onset. It is well known that many disease causing organisms are sensitive to oxidants. Various compounds classifiable as oxides of chlorine such as sodium hypochlorite (NaClO) sodium hypochlorite and chlorine dioxide (ClO2) chlorine dioxide are already widely used as disinfectants. What is novel and exciting here is that Mr. Humble's technique seems: 1) easy to use, 2) rapidly acting, 3) successful, 4) apparently lacking in toxicity, and 5) affordable. If this treatment continues to prove effective, it could be used to help rid the world of one of the most devasting of all known plagues. Especially moving in me is the empathy I feel for anyone with a debilitating febrile illness. I cannot forget how horrible I feel whenever I have caught influenza. How much more miserable it must be to suffer like that again and again every 2 to 3 days as happens in malaria. Millions of people suffer this way year round. 1 to 3 million die from malaria every year mostly children. Thus motivated I sought to learn all I could about the chemistry of the oxides of chlorine. I wanted to understand their probable mechanisms of toxicity towards the causative agents of malaria (Plasmodium species). I wanted to check available literature pertaining to issues of safety or risk in human use.

OXIDANTS AS PHYSIOLOGIC AGENTS

Oxidants are atoms or molecules which take up electrons. Reductants are atoms or molecules which donate electrons to oxidants. I was already very familiar with most of the medicinally useful oxidants. I had taught at numerous seminars on their use and explained their mechanisms of action on the biochemical level. Examples are: hydrogen peroxide hydrogen peroxide , zinc peroxide zinc peroxide , various quinones (e.g. benzoquinone benzoquinone , rhodizonic acid) rhodizonic acid , various glyoxals (e.g. glyoxal glyoxal , methyl glyoxal methyl glyoxal , ozone ozone , ultraviolet light, hyperbaric oxygen , benzoyl peroxide benzoyl peroxide , anodes, artemisinin artemisinin , methylene blue methylene blue , allicin allicin, iodine iodine and permanganate potassium permanganate . Some work has been done using dilute solutions of sodium chlorite (NaClO2) sodium chlorite internally to treat fungal infections, chronic fatigue, and cancer; however, little has been published in that regard.
Low dose oxidant exposure to living red blood cells induces an increase in 2,3-diphosphoglycerate 2,3-diphosphoglycerate levels inside these cells. This attaches to hemoglobin (Hb) in such a way that oxyhemoglobin (HbO2) more readily releases oxygen (O2) regular diatomic oxygen to the tissues throughout the body.
Hyperbaric oxygenation (oxygen under pressure):
  1. is a powerful detoxifier against carbon monoxide;
  2. is a powerful support for natural healing in burns, crush injuries, and ischemic strokes; and
  3. is an effective aid to treat most bacterial infections.

Taken internally, intermittently and in low doses many oxidants have been found to be powerful immune stimulants. Sodium chlorite (NaClO2) sodium chlorite acidified with lactic acid lactic acid as in the product "WF10" has similarly been shown to modulate immune activation. Exposure of live blood to ultraviolet light also has immune enhancing effects. These treatments work through a natural physiologic trigger mechanism, which induces peripheral white blood cells to express and to release cytokines. These cytokines serve as a control system to down-regulate allergic reactions and as an alarm system to increase cellular attack against pathogens.

The procedure as used by Mr. Humble follows: A 28% stock solution of 80% (technical grade) sodium chlorite (NaClO2) sodium chlorite is prepared. The remaining 20% is a mixture of the usual excipients necessary in the manufacture and stabilization of sodium chlorite (NaClO2) powder or flake. Such are mostly sodium chloride (NaCl) ~19% sodium chloride , sodium hydroxide (NaOH) <1% sodium hydroxide , and sodium chlorate (NaClO3) <1% sodium chlorate . The actual sodium chlorite (NaClO2) present is therefore 22.4%. Using a medium caliber dropper (25 drops per cc), the usual administered dose per treatment is 6 to 15 drops. In terms of milligrams of sodium chlorite (NaClO2), this calculates out to 9mg per drop or 54mg to 135mg per treatment. Effectiveness is enhanced, if prior to administration the selected drops are premixed with 2.5 to 5 cc of table vinegar acetic acid or lime juice or 5-10% citric acid citric acid and allowed to react for 3 minutes. The resultant solution is always mixed into a glass of water or apple juice and taken orally. The carboxylic acids neutralize the sodium hydroxide (NaOH) sodium hydroxide and at the same time convert a small portion of the chlorite (ClO2-) sodium chlorite to its conjugate acid known as chlorous acid (HClO2) chlorous acid . Under such conditions the chlorous acid (HClO2) will oxidize other chlorite anions (ClO2-) sodium chlorite and gradually produce chlorine dioxide (ClO2). chlorine dioxide Chlorine dioxide (ClO2) appears in solution as a yellow tint which smells exactly like elemental chlorine (Cl2) chlorine . The above described procedure can be repeated a few hours later if necessary. Considerably lower dosing should be applied in children or in emaciated individuals scaled down according to size or weight. The diluted solution can be taken without food to enhance effectiveness but this often causes nausea. Drinking extra water usually relieves this. Nausea is less likely to occur if food is present in the stomach. Starchy food is preferable to protein as protein quenches chlorine dioxide (ClO2) chlorine dioxide . Significant amounts of vitamin C (ascorbic acid) ascorbic acid must not be present at any point in the mixtures or else this will quench the chlorine dioxide (ClO2) chlorine dioxide and render it ineffective. For the same reason antioxidant supplements should not be taken on the day of treatment. Other side effects reported are transient vomiting, diarrhea, headache, dizziness, lethargy or malaise.
++++++++
 

Activated cells of the immune system naturally produce strong oxidants as part of the inflammatory process at sites of infection or cancer to rid the body of these diseases. Examples are: superoxide (*OO-) superoxide , hydrogen peroxide (H2O2) hydrogen peroxide , hydroxyl radical (HO*) hydroxyl radical , singlet oxygen (O=O) singlet oxygen and ozone (O3) ozone . Another is peroxynitrate (-OONO) peroxynitrate the coupled product of superoxide (*OO-) superoxide and nitric oxide (*NO) nitric oxide radicals.
-OO* + *NO -> -OONO
Yet another is hypochlorous acid (HOCl) hypochlorous acid the conjugate acid of sodium hypochlorite (NaClO) sodium hypochlorite . The immune system uses these oxidants to attack various parasites.
oxidants as ammunition

OXIDES OF CHLORINE AS DISINFECTANTS

All bacteria have been shown to be incabable of growing in any medium in which the oxidants (electron grabbers) out-number the reductants (electron donors). Therefore, oxidants are at least bacteriostatic and at most are bacteriocidal. Many oxidants have been proven useful as antibacterial disinfectants. Hypochlorites (ClO-) sodium hypochlorite are commonly used as bleaching agents, as swimming pool sanitizers, and as disinfectants. At low concentrations chlorine dioxide (ClO2) chlorine dioxide has been shown to kill many types of bacteria, viruses and protozoa. Ozone (O3) ozone or chlorine dioxide (ClO2) chlorine dioxide are often used to disinfect public water supplies or to sanitize and deodorize waste water. Sodium chlorite (NaClO2) sodium chlorite or chlorine dioxide (ClO2) chlorine dioxide solutions are used in certain mouth washes to clear mouth odors and oral bacteria. Chlorine dioxide (ClO2) sanitizes food preparation facilities. Acidified sodium chlorite is FDA approved as a spray in the meat packing industry to sanitized meat. This can also be used to sanitize vegetables and other foods. Farmers use this to cleanse the udders of cows to prevent mastitis, or to rid eggs of pathogenic bacteria. Chlorine dioxide (ClO2) can be used to disinfect endoscopes. Oxidants such as iodine iodine , various peroxides benzoyl peroxide , permanganate potassium permanganate and chlorine dioxide chlorine dioxide can be applied topically to the skin to treat infections caused by bacteria or fungi.

MALARIA IS OXIDANT SENSITIVE

From November 2006 through May of 2007 I spent hundreds of hours searching biochemical literature and medical literature pertaining to the biochemistry of Plasmodia. Four species are commonly pathogenic in humans namely: Plasmodium vivax, Plasmodium falciparum, Plasmodium ovale and Plasmodium malariae. What I found was an abundance of confirmation that, just like bacteria, Plasmodia are indeed quite sensitive to oxidants. Examples of oxidants toxic to Plasmodia include: artemisinin artemisinin , artemether artemether , t-butyl hydroperoxide tertiary butyl hydroperoxide , xanthone xanthone , various quinones (e.g. atovaquone atovaquone , lapachol lapachol , beta-lapachone beta-lapachone , menadione menadione ) and methylene blue methylene blue .

TARGETING THIOLS

Like bacteria, fungi and tumor cells, the ability of Plasmodia to live and grow depends heavily on an internal abundance of reductants. This is especially true regarding thiol compounds also known as sulfhydryl compounds (RSH) a generalized thiol . Thiols as a class behave as reductants (electron donors). As such they are especially sensitive to oxidants (electron grabbers).
Thiols (RSH) such as glutathione glutathione and other sulfur compounds are reactive with sodium chlorite (NaClO2) sodium chlorite and with chlorine dioxide (ClO2) chlorine dioxide . These are the very agents present in Mr. Humble's solution. Possible products of oxidation of thiols (RSH) a generalized thiol using various oxides of chlorine are: disulfides (RSSR) a generalized disulfide , disulfide monoxides (RSSOR) a generalized disulfide monoxide , sulfenic acids (RSOH) a generalized sulfenic acid , sulfinic acids (RSO2H) a generalized sulfinic acid and sulfonic acids (RSO3H) a generalized sulfonic acid .
None of these can support the life processes of the parasite. Upon sufficient removal of the parasite's life sustaining thiols (RSH) a generalized thiol by oxidation, the parasite rapidly dies. A list of thiols (RSH) upon which survival of Plasmodium species heavily depend includes: dihydrolipoic acid dihydrolipoic acid , coenzyme A coenzyme A and acyl carrier protein 4'-phosphopantetheine , glutathione glutathione , glutathione reductase, glutathione-S-transferase, peroxiredoxin, thioredoxin, glutaredoxin, plasmoredoxin, thioredoxin reductase, falcipain and ornithine decarboxylase.
protein thiols - 
note L-cysteine residues
protein disulfides - 
note disulfide bonds
glutathione disulfide cystine

HEME IS AN OXIDANT SENSITIZER

Of particular relevance to treating malaria is the fact that Plasmodial trophozoites living inside red blood cells must digest hemoglobin (Hb) as their preferred protein source. They accomplish this by ingesting hemoglobin (Hb) into an organelle known as the "acid food vacuole". Incidently, the high concentration of acid in this organelle could serve as an additional site of conversion of chlorite (ClO2-) sodium chlorite to the more active chlorous acid (HClO2) chlorous acid or chlorine dioxide (ClO2) chlorine dioxide right inside the parasite. Furthermore, Plasmodia consume 50 to 100 times more glucose than noninfected red blood cells most of which is metabolized to lactic acid lactic acid another known activator of chlorite (ClO2-). Next falcipain a hemoglobin digesting enzyme hydrolyzes hemoglobin protein to release its nutritional amino acids. A necessary byproduct of this digestion is the release of 4 heme molecules heme from each hemoglobin molecule digested. Free heme (also known as ferriprotoporphyrin IX) is redox active and can react with ambient oxygen (O2) regular diatomic oxygen , an abundance of which is always present in red blood cells. This produces superoxide radical (*OO-) superoxide radical , hydrogen peroxide (H2O2) hydrogen peroxide and other reactive oxidant toxic species (ROTS). These can rapidly poison the parasite internally. To protect themselves against this dangerous side-effect of eating blood protein, Plasmodia must maintain a high reductant capacity (an abundance of reduced thiols (RSH) a generalized thiol and NADPH NADPH ) to quench these ROTS. This is their main mechanism of antioxidant defense. Plasmodia must also rapidly and continuously eliminate heme heme , which is accomplished by two methods. Firstly, heme is polymerized producing hemozoin. Secondly, heme is metabolized in a detoxification process that requires reduced glutathione (GSH) glutathione . Therefore any method (especially exposure to oxidants) which limits the availability of reduced glutathione (GSH) will cause a toxic build up of heme and of ROTS inside the parasite cells. Sodium chlorite (NaClO2) and chlorine dioxide (ClO2) (the exact agents present in Mr. Humble's treatment) readily oxidize glutathione (GSH). Therefore, a rapid killing of Plasmodia upon taking acidified sodium chlorite orally should be expected.

OVERCOMING ANTIBIOTIC RESISTANCE WITH OXIDATION

Now the issue of resistance of Plasmodium species to commonly used antiprotozoal antibiotics must be addressed. Quinine quinine , chloroquine chloroquine , mefloquine mefloquine , quinacrine quinacrine , amodiaquine amodiaquine , primaquine primaquine and other quinoline-like antibiotics quinoline all work by blocking the heme heme detoxifying system inside the trophozoites. Many Plasmodial strains against which quinolines have repeatedly been used have found ways to adapt to these drugs and to acquire resistance. Research into the mechanisms of resistance has found that often resistance is accomplished by a meere upregulation of glutathione (GSH) glutathione production and utilization. Consequently oxidizing or otherwise depleting glutathione (GSH) inside the parasite usually restores sensitivity to the quinoline antibiotics. Therefore, protocols combining the use of oxidants with quinolines are under developement and already showing signs of success. In this context let us consider that no amount of intraplasmodial glutathione (GSH) could ever resist exposure to a suffient dose of chlorine dioxide (ClO2) chlorine dioxide . Note that each molecule of chlorine dioxide (ClO2) can disable 1 to 5 molecules of glutathione (GSH) depending on the reaction mechanism.
2(GSH) + 2(ClO2) --> 1(GSSG) + 2(H+) + 2(ClO2-)
or
10(GSH) + 2(ClO2) --> 5(GSSG) + 2(H+) + 2(Cl-) + 4(H2O)

SOME INCOMPATIBILITIES

Acidified sodium chlorite could provide a powerful new opportunity to improve or to restore sensitivity to quinolines quinoline by virtue of its oxidative power. However, quinolines contain secondary amino groups a generalized secondary amine or tertiary amino groups a generalized tertiary amine which react with chlorine dioxide (ClO2) chlorine dioxide in such a way that both could destroy each other. Some possible strategies to resolve this incompatibility are suggested below.
  1. Acidified sodium chlorite could be used as explained above only as a solo therapy.
  2. Quinoline administration could be withheld until after the acidified sodium chorite has completed its action.
  3. Patients already preloaded with a quinoline could stop this, wait a suitable period of time for this to wash out, then administer the acidified sodium chlorite.
  4. The quinoline could remain in use and while the less active sodium chlorite is administered without acid. This should retain plenty of oxidant effectiveness without destroying any quinoline or wasting too much oxidant.
  5. Switch from a quinoline to an endoperoxide (such as artemisinin) or to a quinone (such as atovaquone) before using acidified sodium chlorite, as these may be less sensitive toward destruction by chlorine dioxide.
Similar problems apply to methylene blue methylene blue and many other drugs if they have an unoxidized sulfur atom, a phenol group a generalized monophenol , a secondary amine a generalized secondary amine or a tertiary amine. a generalized tertiary amine Such are reactive with the chlorine dioxide (ClO2) chlorine dioxide component.

REDUCTANT RECOVERY SYSTEMS

Living things possess a recovery system to rescue oxidized sulfur compounds. It operates through donation of hydrogen atoms to these compounds and thereby restores their original condition as thiols (RSH) a generalized thiol .
2 [H] + (RSSR) -> 2(RSH)
This system is known as the hexose monophophate shunt. A key player in this system is the enzyme glucose-6-phosphate- dehydrogenase (G6PDH). glucose-6-phosphate the substrate 
for glucose-6-phosphate-dehydrogenase This enzyme is an essential part of a complex process that produces NADPH NADPH the main provider of reductants to the reductases (enzymes which convert oxidized sulfur compounds back into thiols (RSH) a generalized thiol ). Patients with a genetic defect of G6PDH, known as glucose-6-phosphate-dehydrogenase deficiency disease, are especially sensitive to oxidants and to prooxidant drugs. However, this genetic disease has a benefit in that such individuals are naturally resistant to malaria. They can still catch malaria, but it is much less severe in them, since they permanently lack the enzyme necessary to assist the parasite in reactivating glutathione disulfide (GSSG) glutathione disulfide and other oxidized thiols. Chlorine dioxide (ClO2) chlorine dioxide has been shown to oxidize and denature G6PDH by reaction with the tyrosine L-tyrosine and the tryptophan L-tryptophan residues inside the enzyme. Furthermore, G6PDH is sensitive to inhibition by sodium chlorate (NaClO3) sodium chlorate , another member of the chlorine oxide family of compounds. Sodium chlorate (NaClO3) is a trace ingredient present in Jim Humble's antimalarial solution. Some sodium chlorate (NaClO3) sodium chlorate should also be produced in vivo by a slow reaction of chlorine dioxide (ClO2) with water under alkaline conditions.
2(ClO2) + 2(OH-) -> (ClO2-) + (ClO3-) + H2O
The Plasmodia may attempt to restore any thiols (RSH) a generalized thiol lost to oxidation. However, this becomes more difficult as G6PDH is inhibited by chlorine dioxide (ClO2) chlorine dioxide or by chlorate (ClO3-) sodium chlorate .

TARGETING IRON

While most available literature refers to redox imbalances causing depletion of necessary thiols (RSH) a generalized thiol . Other mechanisms of toxicity of the oxides of chlorine against Plasmodia should also be considered. Oxides of chlorine are generally rapidly reactive with ferrous iron (Fe++) converting it to ferric (Fe+++). This explains why in cases of overdosed exposures to oxides of chlorine such as sodium chlorite (NaClO2) sodium chlorite there was a notable rise in methemoglobin levels. Methemoglobin is a metabolically inactive form of hemoglobin in which its ferrous iron (Fe++) cofactor has been oxidized to ferric (Fe+++). metheme In living things including parasites iron is a necessary cofactor for many enzymes. Thus it is reasonable to expect that any damage to Plasmodia caused by oxides of chlorine is compounded by conversion of ferrous (Fe++) cofactors to ferric (Fe+++) or other alterations of iron compounds. Superoxide dismutase (SOD) inside Plasmodial cells also utilizes iron in its active center. Chlorine dioxide chlorine dioxide also oxidizes manganese (Mn++).

TARGETING POLYAMINES

Other metabolites necessary for survival and growth in tumors, bacteria and parasites are the polyamines. Plasmodia quit growing and die, when polyamines are lacking, or when their functions are blocked. Polyamines are also sensitive to oxidation and can be eliminated by strong oxidants. When oxidized, polyamines are converted to aldehydes a generalized aldehyde , which are deadly to parasites and to tumors. Chlorine dioxide (ClO2) chlorine dioxide is known to be especially reactive against secondary amines a generalized secondary amine . This includes spermine spermine and spermidine spermidine the two main biologically important polyamines.
Thus any procedure, which is successful to oxidize both thiols (RSH) a generalized thiol and polyamines does quadruple damage to the pathogen:
  1. oxidation of the thiol containing protein ornithine decarboxylase L-ornithine substrate 
for ornithine decarboxylase
    inhibits polyamine synthesis;
  2. oxidation of the thiol containing protein S-adenosyl-L-methionine decarboxylase S-adenosyl-L-methionine substrate 
for S-adenosyl-L-methionine decarboxylase
    also inhibits polyamine synthesis;
  3. oxidation of the secondary amines spermidine spermidine and spermine spermidine
    depletes polyamine supplies;
  4. the products of polyamine oxidation are toxic aldehydes a generalized aldehyde .

TARGETING PURINES

Purines purine are essential to many life processes. These molecules have a double ring structure. The rings are heterocyclic being composed of both carbon and nitrogen. The secondary amino nitrogen atoms a generalized secondary amine are vulnerable to reaction with chlorine dioxide (ClO2) chlorine dioxide . Examples of important biologic purines are xanthine xanthine , hypoxanthine hypoxanthine , inosine inosine , guanine guanine and adenine adenine . Guanine and adenine are essential components of DNA and RNA necessary for all genetic functions and for all protein syntheses. Adenine is an essential component of the cofactors NADH NADH , NADPH NADPH , FAD FAD and ATP ATP , necessary for many metabolic functions including oxidation- reduction and energy metabolism. Any purines lost because of chlorine dioxide (ClO2) chlorine dioxide exposure can be readily replaced by host cells. Plasmodia and other apicomplexae are uniquely vulnerable to purine purine deficiency as they lack the enzymes necessary to produce purines for themselves. Instead these must be scavenged from host cells and imported across the plasma membranes of the parasite cells. Drugs are under development to inhibit purine utilization by Plasmodia and are already showing signs of success. Temporarily destroying some of the purines in the blood as should occur upon brief exposure to chlorine dioxide (ClO2) chlorine dioxide in vivo is probably an additional stress that Plasmodia cannot tolerate.

TARGETING PROTEINS

Chlorine dioxide (ClO2) chlorine dioxide is highly reactive with thiols (RSH) a generalized thiol , phenols a generalized monophenol , secondary amines a generalized secondary amine and tertiary amines a generalized tertiary amine . Therefore, proteins composed of amino acids which present these reactive groups are vulnerable to oxidation by this agent. Proteins which present thiol groups as residue(s) of the amino acid L-cysteine L-cysteine 
an amino acid with a thiol group are discussed above under TARGETING THIOLS. L-tyrosine L-tyrosine 
an amino acid with a monophenol group presents a phenol group and is therefore similarly vulnerable. L-tryptophan L-tryptophan 
an amino acid with a secondary amino group , L-histidine L-histidine 
an amino acid with a secondary amino group , L-proline L-proline 
an amino acid with a secondary amino group and 4-hydroy-L-proline 4-hydroxy-L-proline 
an amino acid with a secondary amino group present secondary amino groups which are also especially reactive with chlorine dioxide (ClO2) chlorine dioxide .

SAFETY ISSUES

A remaining concern is safety. So far, at least anecdotally, the dosages of chlorine oxides as administered orally per Jim Humble's protocol have produced no definite toxicity. Some have taken this as often as 1 to 3 times weekly and on the surface seem to suffer no ill effects. To be certain if this is safe more research is warranted for such long term or repeated use. The concern is that too much or too frequent administration of oxidants could excessively deplete the body's reductants and promote oxidative stress. One useful way to monitor this may be to periodically check methemoglobin metheme levels in frequent users. Sodium chlorite (NaClO2) sodium chlorite , as found in municipal water supplies after disinfection by chorine dioxide (ClO2) chlorine dioxide , has been studied and proven safe. Animal studies using much higher oral or topical doses have proven relatively safe. In a suicide attempt 10g of sodium chlorite (NaClO2) taken orally caused refractory methemoglobinemia and nearly fatal kidney failure. Inhalation or aerosol exposure to chlorine dioxide (ClO2) gas is highly irritating and generally not recommended. Special precautions must be employed in cases of glucose-6-phosphate-dehydrogenase deficiency disease, as these patients are especially sensitive to oxidants of all kinds. Nevertheless, oral acidified sodium chlorite solutions might even be found safe and effective in them, but probably will need to be administered at lower doses.

MORE RESEARCH

It is hoped that this overview will spark a flurry of interest, and stimulate more research into the use of acidified sodium chlorite in the treatment of malaria. The above appreciated observations need to be proven more rigorously and published. The biochemistry most likely involved suggests that other members of the phylum Apicomplexa should also be sensitive to this treatment. This phylum includes: Plasmodium, Babesia, Toxoplasma, Cryptosporidium, Eimeria, Theileria, Sarcocystis, Cyclospora, Isospora and Neospora. These pathogens are responsible for widespread diseases in humans, pets and cattle. Other thiol (RSH) a generalized thiol dependent parasites should also be susceptible to acidified sodium chlorite. For example Trypanosoma and Leishmania extensively utilize and cannot survive without the cofactor known as trypanothione. trypanothione Each molecule of trypanothione presents 2 sulfur atoms and 5 secondary amino groups all of which are vulnerable to oxidative destruction from chlorine dioxide (ClO2) chlorine dioxide . Chlorine dioxide (ClO2) has been proven to be cidal to almost all known infectious agents in vitro using remarkably low concentrations. This includes parasites, fungi, bacteria and viruses. The experiences noted above imply that this compound is tolerable orally at effective concentrations. Therefore extensive research is warranted to determine if acidified sodium chlorite is effective in treating other infections. We may be on the verge of discovering the most potent and broad spectrum antimicrobial agent yet known. Special thanks go to Jim Humble for his willingness to share his discovery with the world.

by Thomas Lee Hesselink, MD


References are available upon request.
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Link zum deutschen Text:
http://meine-aura.de/malaria/main2.php?p=Chlordioxid3
Die Oxidationsvorgänge im Zusammenhang mit der Applikation von Chlordioxid


Vorwort:
Die folgenden Informationen beziehen sich auf den Bericht des amerikanischen Arztes MD Thomas Lee Hesselink
Der Bericht beruht auf der Analyse von 162 Literaturstellen. Anlass für seine Untersuchungen waren die Erfolge bei der Anwendung eines Produktes zur Erzeugung von Chlordioxid.
Anmerkung: Die „Ich-Form“ weist auf die Meinung von Thomas Lee Hesselink hin.
Es wird damit erstmalig eine Zusammenfassung der mit Chlordioxid im Zusammenhang stehenden Oxidationsvorgänge im Menschen gegeben. Mit diesen folgenden Beschreibungen können die in den WHO-Guidelines 2006 Werte zur toxischen Wirksamkeit von Chlordioxid hinsichtlich Bakterien, Viren und Parasiten plausibel begründet werden.
Besonders bemerkenswert sind Schlussfolgerungen von T.L. Hesselink bezüglich der Wirkung von Chloriten und Chloraten auf das Absterben von Parasiten.
Diese Darlegungen stehen im offensichtlichen Gegensatz zu der geläufigen Auffassung, dass Chlorite und Chlorate grundsätzlich für den menschlichen Organismus schädlich seien. Es scheint sich der Grundsatz „ Dosis facid venenum- Die Dosis macht das Gift“ zu bestätigen. Wenn Chlorite und Chlorate lediglich Gift für die Bakterien, Viren und Parasiten wären, dann ist das positiver und weiterhin untersuchungswürdiger Effekt.
Der Bericht kann all denen nützlich sein, die sich tiefere Klarheit über die ganzheitlichen desinfizierenden Wirkungen von Chlordioxid verschaffen wollen. Unabhängig von den Wirkungen von Chloridoxiden in den Stoffwechselprozessen der Lebewesen, werden durch Thomas Lee Hesseling wesentliche Argumente zur Anwendung von Chlordioxid für die Sicherung der Qualität des Wassers für den menschlichen Verzehr beschrieben. Es zeigt einen Weg zur Aufbereitung des Wassers für den menschlichen Verzehr in den subtropischen und tropischen Gebieten so zu behandeln.
Es folgen jetzt die zusammengefassten Erkenntnisse von Thomas Lee Hesselink:
1. Oxidationsmittel als physiologische Wirkstoffe
Mit den meisten anderen bekannten medizinisch nützlichen Oxidationsmitteln war ich bereits vertraut. Genannt seien hier:
Wasserstoffperoxid, Zinkperoxid, verschiedene Chinone, verschiedene Glyoxale, Ozon, ultraviolettes Licht, hyperbarer Sauerstoff, Benzylperoxid, Artemisinin, Methylenblau, Allizin, Jod, Permanganat.
Ich habe zahlreich Seminare darüber gehalten, wie man sie anwendet und wie sie auf biochemischer Ebene funktionieren.
Oxidationsmittel sind Atome oder Moleküle, die Elektronen aufnehmen. Reduktionsmittel dagegen sind Atome oder Moleküle, die Elektronen an Oxidationsmittel abgeben.
Setzt man lebende rote Blutkörperchen einer geringen Menge eines Oxidationsmittels aus, ändert sich die Oxyhämoglobin-Aktivität ( Hb-O2) dahingehend, dass mehr Sauerstoff in das Gewebe abgegeben wird. Hyperbare Oxygenierung ( unter erhöhten Druck gesetzter Sauerstoff):
- wirkt effektiv entgiftend gegen Kohlenstoffmonoxid;
- unterstützt die natürlichen Heilungsprozesse bei Verbrennungen, Quetschungen und ischämischen Schlaganfall immens und ist ein wirkungsvolles Mittel gegen bakterielle Infektionen.
- Innerlich, periodisch und in kleinen Dosen angewandt, stimulieren viele Oxidationsmittel das Immunsystem sehr effektiv. Eine ähnliche Wirkung erzielt man, wenn man lebende Blutzellen ultraviolettem Licht aussetzt.
Diese Behandlungsmethoden wirken durch einen natürlichen physiologischen Impulsmechanismus, der periphere weiße Blutkörperchen dazu anregt, Zytokine zu bilden. Diese Zytokine dienen als Alarmsystem und sorgen dafür, dass die Zellen vermehrt Krankheitserreger angreifen und allergische Reaktionen verhindert werden.
Aktivierte Zellen des Immunsystems produzieren im Rahmen eines Entzündungsprozesses wirksame natürliche Oxidationsmittel, um den Körper an Infektions- oder Krebsherden von der jeweiligen Krankheit zu befreien.
Eines dieser natürlichen Abwehr-Oxidationsmittel ist Wasserstoffperoxid. Ein anderes ist Peroxynitrat, ein Produkt aus Superoxid-Radikalen und Stickoxid-Radikalen. Ein weiterer ist hypochlorige Säure, die konjugierte Säure von Natriumhypochlorit.
2. Oxidationsmittel als Keimtöter
Verschiedene starke Oxidationsmittel sind als Desinfektionsmittel weit verbreitet. Es ist bewiesen, dass Bakterien nicht in der Lage sind, sich in einem Medium auszubreiten, das mehr ( Elektronen aufnehmende) Oxidationsmittel als ( Elektronen abgebende ) Reduktionsmittel enthält. Somit sind Oxidationsmittel bakteriostatisch, wenn nicht gar bakteriozid.
Einige Oxidationsmittel wie Jod, diverse Peroxide und Permanganat werden oberflächlich auf der Haut angewandt, um Infektionen vorzubeugen, die von Bakterien oder Pilzen ausgelöst werden. Chlordioxid wird ähnlich verwendet.
Hypochlorite kommen vor allem als Bleichmittel zum Einsatz, dienen aber auch zur Entkeimung von Schwimmbädern und als Desinfektionsmittel. Chlordioxid wie auch Ozon werden als keimtötende Mittel zur Wasseraufbereitung genutzt.
Natriumchlorit-Lösungen werden schon lange als Mundwasser gegen Mundgeruch und Bakterien im Mundraum verwendet. Mit Säure versetztes Natriumchlorit ist von der FDA in der Fleischverpackungsindustrie als Spray zur Desinfektion von Fleisch zugelassen. Landwirte benutzen das Mittel, um Kuheuter zu reinigen und so Mastitis vorzubeugen und um Eier von krankheitserregenden Bakterien zu reinigen. Chlordioxid tötet zudem viele Viren ab. Mit angesäuertem Natriumchlorit kann man sogar Gemüse keimfrei machen. Es wurden Versuche unternommen, mittel oral verabreichter Natriumchlorit-Lösungen Pilzinfektionen, chronische Müdigkeit und Krebs zu behandeln. In dieser Hinsicht ist leider nur sehr wenig in der Literatur veröffentlicht worden.
3. Malaria ist anfällig für Oxidationsmittel
Von November 2006 bis Mai 2007 habe ich viele 100 Stunden damit zugebracht, biochemische und medizinische Literatur nach der biochemischen Funktionsweise von Plasmodien zu durchsuchen. Vier Spezies sind für den menschlichen Körper pathogen:
- Plosmodium vivax
- Plasmodium falciparum
- Plosmodium ovale
- Plasmodium malariae.
Dabei stieß ich auf ein Fülle von hinweisen darauf, dass Plasmodien, ebenso wie Bakterien anfällig gegenüber Oxidationsmitteln sind.
Schädlich für Plasmodien sind beispielsweise: Artemisinin, Atovaquon, Menadion und Methylenblau.
Zudem hängt das Wachstum und Überleben von Plasmodien, wie auch von Bakterien und Tumorzellen, stark davon ab, ob genügend Thiol-Verbindungen vorhanden sind.
Thiole sind auch bekannt als Sulhydrylgruppen (RSH) und verhalten sich als Gruppe wie ( Elektronen abgebende ) Reduktionsmittel. Das macht sie höchst empfindlich gegenüber Oxidationsmitten. Sie reagieren leicht mit Chloroxiden und dazu zählen auch Natriunchlorit und Chlordioxid, eben die Wirkstoffe in Humbles Lösung.
Wenn Thiole mit Chloroxiden (so auch Chlordioxid) oxidieren, kommen u.a. folgende Stoffe heraus: Disulfid (RSSR), Disulfidmonooxid (RSSOR), Sulfensäure (RSOH), Sulfinsäure(RSO2H), Sulfonsäure (RSO3H). Alle diese Stoffe entziehen dem Parasiten die Lebensgrundlage.
Sind durch die Oxidation die für den Parasiten lebenswichtigen Thiole vernichtet, dann stirbt dieser.
Zu den für die Plasmodien-Spezies überlebensnotwendigen Thiolen gehören: Liponsäure und Dihydroliponsäure, das Coenzym A und das Acyl-Trägerprotein, Glutathion, Glutathion-Reduktase, Glutathionoxin, Plasmoredoxin, Thioredoxin-Reduktase,Ornithin-Decarboxylase, und Falcipain.
4. Häme als Sensibilisatoren von Oxidationsmitteln
Von besonderer Bedeutung für die Behandlung von Malaria ist, dass die bevorzugte Proteinquelle der plasmodialen Trophozoiten im Inneren der roten Blutkörperchen Hämoglobin ist. Dabei nehmen sie das Hämoglobin in eine Organelle auf, die sich „saure Nahrungsvakuole“ nennt. Die hohe Säurekonzentration in dieser Organelle könnte zusätzlich zur Umwandlung von Chlorit in das weit aktivere Chlordioxid beitragen, und zwar im Inneren des Parasiten.
Als nächstes hydrolisiert Falcipain ( ein Hämoglobin verdauendes Enzym) das Hämoglobin-Protein und setzt dessen nahrhafte Aminsäuren frei.
Ein wichtiges Nebenprodukt dieses Verdauungsprozesses ist, dass aus jedem verdauten Hämoglobin-Molekül vier Häm-Moleküle freigesetzt werden.
Freie Häm-Moleküle (auch Ferriprotoporphyrin genannt) sind redoxaktiv und können daher mit dem sie umgebenden Sauerstoff reagieren, von dem in roten Blutkörperchen immer reichlich vorhanden ist. Daraus entstehen Superoxid-Radikale, Wasserstoffperoxid und andere reaktive toxische Arten von Oxidationsmitten. Diese vergiften den Parasiten von innen heraus. Um sich selbst vor dem gefährlichen Nebeneffekt des Blutprotein-Konsums zu schützen, müssen Plasmodien permanent und schnell Häme eliminieren.
Das wird auf zwei Wegen erreicht: Zum einen werden Häm-Moleküle polymerisiert und bilden Hämozoin. Zum anderen werden Häme in einem Entgiftungsprozess abgebaut, für den reduziertes Glutathion (GSH) nötig ist.
Weil Herr Humble genau diese zwei Wirkstoffe in seinem Mittel verwendet, ist nur wahrscheinlich, dass der bereits beobachtete Effekt -das Absterben von Plasmodien- auch hier eintritt.
Daher sorgt alles, was verhindert, das der Parasit an reduziertes Glutathion gelangt( auch der Kontakt zu Oxidationsmitteln), in den Zellen des Parasiten für einen Stau an toxischen Häm-Molekülen. Da Natriumchlorit und Chlordioxid Glutathion oxidieren, unterbinden sie den Entgiftungsprozess des Parasiten.
5. Überwindung von Antibiotika-Resistenz mittels Oxidation
In diesem Zusammenhang muss auch die Resistenz der verschiedenen Plasmodien-Spezies gegenüber den gebräuchlichen antiprotozoalen Antibiotika angesprochen werden. Quinin, Chloroquin, Mefloquin und andere Chinolin-Antibiotika wirken dadurch, dass sie das Häm-Entgiftungssystem in den Trophozoiten blockieren. Viele Plasmodien-Stämme, gegen die wiederholt mit Chinolin vorgegangen wurde, haben einen Weg gefunden sich anzupassen und eine Resistenz zu entwickeln. Jüngste Forschungsarbeiten haben jedoch gezeigt, dass der Mechanismus hinter der entwickelten Resistenz, lediglich darin besteht, dass vermehrt Glutathion produziert und eingesetzt wird. Diese Arbeiten haben ebenfalls nachgewiesen, dass die Parasiten wieder auf Quinolin-Antibiotika ansprechen, sobald das Glutathion oxidiert oder anderweitig vermindert wird. Einige Versuche, bei denen man Oxidationsmittel parallel zu Quinolinen eingesetzt hat, haben bereits erste Erfolge gezeitigt. Hierbei gilt es zu berücksichtigen, dass keine noch so große Menge an Glutathion (GSH) in den Plasmodien je gegen eine genügend hohe Dosis Chlordioxid bestehen könnte. Man beachte, dass jedes Chlordioxid-Molekül je 5 Glutathion-Moleküle unschädlich machen kann.
Lebewesen besitzen ein Wiedergewinnungssystem, durch das sie oxidierte Schwefelverbindungen wiedergewinnen können. Dabei werden Wasserstoffatome an diese Schwefel-Verbindungen abgegeben und so deren ursprünglicher Zustand als Thiole wiederhergestellt.
Das Enzym Glukose-6-Phosphat-Dehydrogenase (G6PDH) spielt hierbei eine Schlüsselrolle. Patienten mit einem genetisch bedingten G6PDH-Defekt, besser bekannt als Glukose-6-Phosphat-Dehydrogenase-Mangel, reagieren besonders empfindlich auf Oxidationsmittel und prooxidative Medikamente. Diese genetisch bedingte Erkrankung hat allerdings den Vorteil, dass die Betroffenen gemeinhin resistent gegen Malaria sind. Zwar können auch sie erkranken, doch verläuft die Erkrankung bei ihnen weit weniger schlimm, da sie nicht über eine genügende Menge an dem Enzym verfügen, dass der Parasit braucht, um das Glutathion zu reaktivieren.
Zudem wird G6PDH leicht durch Natriumchlorat gehemmt, ein weiteres Mitglied der Familie der Chloroxid-Verbindungen. Natriumchlorat ist in geringem Maße auch in Jim Humbles Anti-Malaria-Lösung enthalten. Unter leicht alkalischen Bedingungen dürfte sich ein wenig Natriumchlorat auch in vivo als Folge der langsamen Reaktion von Chlordioxid und Wasser bilden. Die Plasmodien versuchen zwar, das Glutathion zu ersetzen, das bei der Oxidation verloren geht. Wenn G6PDH aber durch Chlorat gehemmt wird, ist dies sehr schwer, wenn nicht gar unmöglich.

6. Die Bedeutung von Eisen
Obgleich ein Grossteil der verfügbaren Literatur sich allein auf das gestörte Redox-Gleichgewicht bezieht, das zu einem Mangel an Thiolen führt, sollten auch andere toxische Mechanismen berücksichtigt werden, mit denen Chloroxid gegen Plasmodien vorgeht. Chloroxide (z.B.:Chlorite) reagieren für gewöhnlich mit zweiwertigem Eisen. Das erklärt, warum es beim Kontakt zu großen Mengen Chloroxiden, wie z.B. Natriumchlorit, zu einem deutlichen Anstieg des Methämoglobin- Spiegels kommt. Methämoglobin ist eine den Stoffwechsel nicht beeinflussende Form des Hämoglobins, in der der Cofaktor zweiwertiges Eisen zu dreiwertigem Eisen oxidiert ist. Viele Enzyme in Lebewesen, auch in Parasiten, verwenden Eisen als Cofaktor. Daher ist anzunehmen, dass jede Schädigung der Plasmodien durch Chloroxide (Chlorite, Chlorate) von der Wandlung der zweiwertigen zu dreiwertigen Eisen-Cofaktoren begleitet wird.
7. Die Bedeutung der Polyamine
Weitere Metaboliten, die Tumore, Bakterien und Parasiten zum Wachstum und Überleben brauchen, sind Polyamine. Fehlen diese, können Erreger nicht mehr wachsen, sie sterben. Auch Polyamine reagieren leicht auf Oxidation und lassen sich durch starke Oxidationsmittel zerstören.
Wenn Polyamine oxidieren, verwandeln sie sich in Aldehyde, die wiederum tödlich für Parasiten und Tumorzellen sind.
Somit richtet alles, was Polyamine oxidiert, doppelten Schaden an den Krankheitserregern an. Man weiss, dass gerade Chlordioxid besonders heftig mit sekundären Aminen reagiert. Zu den sekundären Aminen zählen auch Spermien und Spermiden, die aus biologischer Sicht beiden wichtigsten Polyaminen.
Quelle:
1) Jim Humble ; MMS-Der Durchbruch; Deutsche Erstausgabe 2008,Mobiwell-Verlag, Potsdam 2008, Anhang 1, S.186-204)
2) http://www.healthsalon.org/309/thomas-lee-hesselink-md-writes-on-mms-and-sodium-chlorite/
3) http://www.npi.gov.au/database/substance-info/profiles/21.html
Anmerkung:
Nach meinen weltweiten Recherchen kann der Bericht von Thomas Lee Hesseling zu den Oxidationsvorgängen im Zusammenhang mit Chlordioxid als besonders wertvoll eingestuft werden. Er stützt die Ausführungen in dem Arbeitsblatt „ Informationen zu Haftungsrisiken bei der Trinkwasserversorgung“ und vertieft die Applikation von Chlordioxid im allgemeinen und im besonderen zur mikrobiologisch unbedenklichen Herstellung von Wasser für den menschlichen Verzehr. Damit ist Chlordioxid auch in der Getränkeindustrie ( z.B: Coca-Cola) ein zu favorisierendes Mittel zur Desinfektion der Anlagen und Geräte und des durchfließendes Wassers, das für den menschlichen Gebrauch bestimmt ist.
(Dr.-Ing. Wolfgang Storch)
Mai 2009