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Post by questionhair on Sept 14, 2006 13:33:22 GMT -5
In case the link breaks in the future - this is important: ============================================== This is topic Updated Nutshell...12/02/05 for newbies in forum Medical Questions at LymeNet Flash. To visit this topic, use this URL: flash.lymenet.org/scripts/ultimatebb.cgi?ubb=get_topic;f=1;t=039471-------------------------------------------------------------------------------- Posted by Marnie (Member # 773) on 02 December, 2005 02:47 PM : (1) The genetic analysis of Bb indicates it has a 60 kDa pyrophosphate dependent PFK (phosphofructokinase) enzyme. PMID: 12015149 (www.pubmed.com) (2) The enzyme, PFK, is “rate limiting” for glycolysis (using glycogen, not oxygen, to supply energy). And we know Bb is anaerobic – does not need oxygen. It wants/needs sugar. PMID: 10689623 (www.pubmed.com) PMID: 1832860 (www.pubmed.com) (3) PFK is INhibited by Mg-ATP (et al). (Most ATP is bound to Mg.). Insulin ACTIVATES it. www.geocities.com/doctor_uae/carbohydrates.htm www.mcw.edu/student/mcwsa/files/biochem22.doc www.eimb.relarn.ru/eimb/3nature.htm www.apjohncancerinstitute.org/newsletter-old2.htmwww.lowcarbluxury.com/newsletter/lclnewsvol03-no04-pg2.html (4) Bb follows the cholesterol/ mevalonate / isoprenoid pathway. It has another enzyme: acetyl-CoA C-acetyltransferase. Cholesterol is needed to form the myelin sheath, the insulation around our nerves. In MS, this sheath is damaged. (Rohmer 1999; Kim et al. 2000; Wilding et al. 2000a, b). or proteinscience.org/cgi/content/full/13/3/687 www.sbc.su.se/~anna/PhylProM/families_with_members_in_profile/gi1652965.html web.indstate.edu/thcme/mwking/cholesterol.html adams.mgh.harvard.edu/Reeves/workingresearch2.htm (5) Mg (and statin drugs) INactivate the enzyme 5-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) which then reduces mevalonate, the first step in the cholesterol pathway. www.lef.org/whatshot/2004_11.htm Neurol India 2003;51:211-214 The above suggests that intracellular Mg levels play a critical role in regaining control of the glycolysis and cholesterol pathways which are impacted by this pathogen. (6) Cancer doctors at a Romanian hospital found a very “significant” drop in Mg levels early on in 2 lyme patients. By restoring their magnesium levels, they were cured of lyme disease. Please note: this was caught early. www.coldcure.com/html/2003-mag-abstracts.pdf It is on page 79. It is “noted” here: PMID: 14979639. And here: www.ad-astra.ro/isi/topic_articles.php?topic_id=IA Sometimes, but not always, the coldcure website is hard to get into. So, I will post the abstract in its entirety here: Lyme disease and magnesium deficiency V. CRISTEA - Department of Immunopathology, Medical Clinic III, "Iuliu Hatieganu" University of Medicine and Pharmacy, MONICA CRIAN - Department of Immunology, "Ion Chiricu" Oncological Institute, Cluj-Napoca, Romania V. CRIAN - ITEM-Paneuro Group. vlaicu@.m@if..c;!ntci,rQ During the period April 2001 - January 2003, we had under observation two cases, in which the presence of both IgM and IgG antibodies to Borrelia burgdorferi was serologically confirmed at high titers. In both cases, clinical manifestations were similar: shivering, fever, headache, articular and right hypochondrium pain, and objectively - tachycardia and erythema migrans - these elements being important for the formulation of Lyme disease suspicion. Humoral tests showed: significantly increased ESR, leukocytosis with PMN predominance, intensely positive PCR (for B. Burgdorferi DNA) and significant magnesium deficiency (1.20 mEq/L, 1.33 mEq/L, respectively). A large spectrum of antibiotics with both oral and parenteral administration has been so far used in the treatment of Lyme borreliosis. Among the most frequently used are tetracyclines, betalactamides and cephalosporins. The decision to initiate antibiotic therapy can be difficu1t because in the majority of the cases acute infection is self-limited. Asymptomatic patients, in whom laboratory examinations sustain the diagnosis of Lyme disease, should be treated in order to prevent rnfection dissemination. Since in the first case antibiotic therapy alone did not lead to the expected results, magnesium derivatives were also associated. In both cases, following combined therapy, symptomatology significantly improved at 14 days, and laboratory examinations were restored to normal values after 6-8 weeks - disappearance of IgM to B. Burgdorferi and significantly increased magnesemia (1.74 mEq/L, 1.72 mEq/L, respectively) We believe that in certain diseases, Mg deficiency can cause a decrease in immune response. The appearance of recurrences, which are frequently reported in the literature, in spite of adequate antibiotic therapy, could represent an argument for this. This is why the use of Mg derivatrves in therapy can represent an immunostimulating factor. The peculiarities of the cases are the following: 1. Patients had in addition to fever, articular pain and erythema migrans, Mg deficiency 2. The supplementation of therapy with Mg derrvatives had an immediate beneficial effect that was maintained in time. As a conclusion at this stage, we consider that in the acute phase of Lyme borreliosis there is a significant Mg consumption and the introduction in therapy of such preparations is recommended and beneficial. (7) When Mg levels drop, this impacts the number and “health” of our antibodies. Since the Western Blot test measures antibodies, this may be why the testing is inaccurate (assuming it only measures healthy antibodies). The antibody specific to Bb is damaged – the “fab” portion. PMID: 1093189 (www.pubmed.com) PMID: 9125579 (www.pubmed.com) (8) It takes Mg and Ca (calcium) to make completely HEALTHY antibodies. www.mdschoice.com/elements/elements/major_minerals/magnesium.htm
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Post by questionhair on Sept 14, 2006 13:34:07 GMT -5
(9) When Mg levels drop, this has a huge impact on the number of free radicals, inflammation, thymus involution, eye damage, bone loss, mitochondrial damage and so on… PMID: 10615213 (www.pubmed.com) PMID: 9558736 (www.pubmed.com) PMID: 11781153 (www.pubmed.com) www.mdschoice.com/elements/elements/major_minerals/magnesium.htm PMID: 10488476 (www.pubmed.com) J Nutr. 2004 Jan;134(1): 79-85 (10) When Mg levels drop, calcium tries to go into the cells. This triggers TNF alpha – a proinflammatory cytokine and angiotensin II. PMID: 8390527 (www.pubmed.com) (11) TNF alpha has many jobs. In fact, it is protective and beneficial. www.Hopkins-arthritis.som.jhmi.edu/edu/acr2003/ra-treatments.htmlwww.dscmt.univ.trieste.it/text/curriculum/containerbiblio.htmPMID: 10092616 (www.pubmed.com) www.hdlighthouse.org/see/immune/tnf.htmwww.lef.org/protocols/prtcl-128a.shtmlwww.diabetesincontrol.com/issue166/item1.shtml www.cell-research.com/991/991-syf1.html PMID: 9195931 (www.pubmed.com) PMID: 12522038 (www.pubmed.com) PMID: 14704297 (www.pubmed.com) www.saem.org/download/01kline.pdfGastroenterology 2004; 126: 840-848,917-919 www.joimr.org/phorum/read.php?f=2&I=38&t=38PMID: 8537658 (www.pubmed.com) PMID: 15958074 (www.pubmed.com) (12) The antibiotics may modulate the immune system response. Antimicrob Agents Chemother. 1997 January; 41 (1): 117–121 PMID: 8331300 (www.pubmed.com) (13) H2O2, hydrogen peroxide, is a known microbicide – capable of killing many/most pathogens. We actually make H2O2 all the time inside our cells and one of our “beneficial bacteria” in our intestine also makes this, but H2O2 is quickly broken down by an enzyme called catalase because it is not healthy for our cells to remain acidic. Bb is H2O2 “resistant”. www.news-medical.net/?id=9820 www.medscape.com/viewarticle/418448 (you can join medscape then access) PMID: 11687735 (www.pubmed.com) (14) Bb does NOT contain the enzyme catalase. www2.lymenet.org/domino/abstract.nsf/0/da835aef57144e6a0525657d0005cc3e?OpenDocument (15) In 2001, an Italian by the name of Dr. Valletta, got a U.S. patent titled: Magnesium For Autoimmune. He cured RA, ulcerative colitis and invasive cancer in 6 months using Mg pyrophosphate and sublingual B6. To read the patent, # 6,248,368 go to our government patent website and type in the number. (16) We are using a Mg-peroxide solution as an antibacterial agent for clothing. This is also a U.S. patent (# 5,656,037). To read about it, once again go to our government patent website and type in the number. (17) Co-infections complicate the healing process, especially the co-infection with the protozoan, babesia. But in the 1970s, in Germany, vets cured neuro babesia in dogs using IV sodium bicarbonate. The dogs were acidotic and responded surprisingly well to an alkaline infusion. www.sodbrennen-welt.de/science/1976/1976_4617.htm (18) If coinfected with ehrlichiosis = impairment to mount strong immune defense PMID: 16412057 (19) Which strain of Bb one has encountered may impact the severity. PMID: 16405291 (20) IL-10 limits potentially damaging CNS inflammation. PMID: 16419089 (21) IVIG has been used to successfully treat a Bb-babesia infected patient, but the abstract was removed from pubmed. It was # 13680780. This is a very expensive treatment. Once again, please note: to make HEALTHY antibodies (immunoglobulins), we must have enough Mg and Ca. To read this article, one can go directly to the source: Arch Phys Med Rehabil. 2003 Sep;84(9):E34-E35. www.mdschoice.com/elements/elements/major_minerals/magnesium.htm (22) Lyme can cause uveitis due to an overproduction of proinflammatory cytokines. It can also cause meningitis. PMID: 16398326 and PMID: 16396843 (23) Antibiotics deplete vital nutrients and destroy beneficial bacteria which in turn make many nutrients for us. Unfortunately, most doctors do not remind patients that it is vital to restore the beneficial bacteria (take probiotics) when taking antibiotics. For a graph, go to this website and click on antibiotics: www.thechiropracticvillage.com/id140.htm www.phototour.minneapolis.mn.us/candida/ www.probiohealth.com/ Search: “metagenics probiotics” Gut 2004;53:694-700,620-622. (24) Mg is needed as a growth factor for the beneficial bacteria, lactobacilli. www.emdchemicals.com/analytics/Micro_Manual/TEDISdata/prods/1_10660_0500.html (25) We make hydrogen from acids which react with magnesium/other positive charges. CoQ10 carries hydrogen into the cells. CoQ10 levels are impacted due to the decline of many nutrients, especially B6 and magnesium. www.coursework.info/i/67.html www.msgtruth.org/why.htm www.akins.com/hh/co_q10.htm Astrophys. J. 589, L29; L89 (2003) www.lef.org/magazine/mag2001/oct2001_report_coq10_01.html www.globalnutrients.net/NutraceuticalsINDEX.htm PMID: 11401418 (www.pubmed.com) www.curezone.com/foods/coenzyme_q10.htm www.newswithviews.com/Howenstine/james2.htm www.lef.org/abstracts/codex/coq10_index.htmwww.americanlongevity.net/misc/CoQ10_000.php (26) With a Mg deficiency, this puts persons at risk for cancer. Our NK (natural killer cells) need Mg and Ca to do their job. This is our first line of defense against cancer. The following is no longer able to be linked, but since it was “cut and paste” note from a college lecture, I will assume it is “common knowledge” for those studying biochemistry: “Antibody Dependent Killer (K) and Natural Killer (NK) cells (ASCC) kill by extracellular cytotoxicity by binding to a target cell and secreting cytolysins which unidirectionally kill the target cell. Once the target is bound by an NKAR and no NKIR is activated, the cytotoxic reaction occurs. The interaction of cell adhesion molecules between NK and the target cell may tighten the attachment. The first step is a MAGNESIUM DEPENDENT movement of the cytoplasmix organelles (Golgi and granules) of the NK cell to face the target cell. The secretion of the granule contents into the intercellular space is a CALCIUM DEPENDENT step that results in the preferential insertion of perforin pores into the target cell membrane.” See also: www.mnwelldir.org/docs/immune/immune1.htm www.1stvitality.co.uk/az/magnesium/ www.expage.com/energizeyourlife13(27) As stated above (4) Bb uses acetyl-CoA (part of the cholesterol pathway). This nutrient is also needed to make the neurotransmitter acetylcholine. When one neurotransmitter is effected, it impacts the others. The body’s BALANCE is off. Serotonin (which ultimately converts to melatonin) and dopamine (cells damaged by free radicals) are impacted. This can lead to neuro symptoms (depression, sleep problems) and more than one neurological disease. We need nutrients to make the neurotransmitters and neurohormones. web.indstate.edu/thcme/mwking/nerves.html www.benbest.com/science/anatmind/anatmd10.html www.chemicalbalance.com/part_one_manual.htm (28) Bb locks onto a heparin receptor. It may be using fibrin to cloak itself and thus avoid detection/destruction. Magnesium may reduce insoluble fibrin. www-heparin.rpi.edu/papers/PDFfiles_2000_present/CarbBased%20Drug%20Discovery.pdf 64.233.167.104/search?q=cache:Ay2HJ8b6iEQJ:medicine.plosjournals.org/perlserv/%3Frequest%3Dread-response%26doi%3D10.1371/journal.pmed.0020098+Magnesium+may+reduce+insoluble+ fibrin+levels+by+displacing+calcium+in+the+coagulation+process&hl=en (29) Bb needs CHOLINE! It is taking this nutrient and others from us. www.sbc.su.se/~anna/PhylProM/families_with_members_in_profile/gi1652965.html mic.sgmjournals.org/cgi/reprint/150/2/391 (30) Bb contains a PKC inhibitor. This is a protein kinase C inhibitor. Protein kinase C inhibitors compete with Mg-ATP. PKC inhibitors cause cell death. When the body is exposed to this inhibitor, Mg is dumped quickly. PMID: 8978084 www.biochemj.org/bj/351/0095/3510095.pdf (32) Bb breaks down carbohydrates into toxic acetate and ethanol. This reduces Ca and additional Mg. www.bact.wisc.edu/Microtextbook/index.php?name=Sections&req=viewarticle&artid=110&page=1 www.emedicine.com/ped/topic2715.htm
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Post by questionhair on Sept 14, 2006 13:35:20 GMT -5
(33) H16 is in several chemical formulas that seem to help fight lyme disease such as: acetylcholine, melatonin, warfarin, Rocephin, thiamine (B1 – in Valletta’s patent…is part of pyrophosphate), ATP, etc. This is a very odd co-incidence and I wish I understood why 16 hydrogen atoms is so important. www.fas.org/nuke/guide/usa/doctrine/dod/fm8-9/3appb.htm (It may be that H16 in the molecular formulas is related to “PKC inhibitors”.) (34) Ron S. Ronimus, Xuewei Liu, Russell S. Roberson, Charles E. McKenna, and Hugh W. Morgan, “Inhibition of the Active Pyrophosphate-dependent Phosphofructokinases from the Syphilis Pathogen Treponema Pallidum and Lyme Disease Spirochete Borrelia Burgdorferi Using Bisphosphonates”, Biochem. Pharmacol., Accepted, 2005. www.ntu.edu.sg/home/xuewei/ (see #4) Bisphosphonates are a family of drugs used to prevent and treat osteoporosis. www.osteoporosis.ca/english/About%20Osteoporosis/Drug%20Treatments/Bisphosphonates/default.asp?s=1 By definition: Bisphosphonates, analogs of a naturally occurring compound, pyrophosphate, that serves to*regulate calcium*, are drugs that prevent bone breakdown. Bisphosphonates bind permanently to the surfaces of the bones and slow down the osteoclasts (bone-eroding cells). This allows the osteoblasts (bone-building cells) to work more effectively. www.osteoporosis.ca/english/About%20Osteoporosis/Drug%20Treatments/Bisphosphonates/default.asp?s=1 Since drug companies cannot market pyrophosphate because it is a naturally occurring compound, they market a very similar man-made drug. The naturally occurring compound, pyrophosphate, is nothing more than thiamine (B1) and phosphorous. lpi.oregonstate.edu/infocenter/vitamins/thiamin/ But, Magnesium is necessary for the conversion of thiamine to its biologically active form, thiamine pyrophosphate. www.farmacopia.net/nutrient_danger.html Some cell types have H+ pumps which are driven by pyrophosphate. www.uni-konstanz.de/FuF/Bio/research/Arbeitsgruppen/Plattner/Homepage/PDF/Acidocalcisome%20Herpetomonas.pdf Magnesium pyrophosphate, a known inhibitor of the kinase reaction (M. G. Thomas and J. C.Escalante-Semerena, unpublished results… www.biochem.wisc.edu/rayment/publications/pub_pdfs/100_119/108rayment99_thompson.pdf (Remember, Bb contains a PKC – protein kinase C inhibitor.) And, The active coenzyme form of B-1, thiamin pyrophosphate (TPP), is necessary for energy production and is essential for the formation of *acetylcholine*, a major neurotransmitter. www.anvaripour.com/b1.html However, the Rx. bisphosphonates do not come without risk, such as a chance for a serious jaw bone disease, uveitis, and an alteration in the expression of the proteins, TNF alpha and CRP (sources in disagreement). From PERSONAL knowledge, the combination of Humira to reduce TNF alpha AND Foxamax in one person -> MORE TNF alpha and CRP. www.news-medical.net/?id=6844 www.lareb.nl/documents/kwb_2002_4_alend.pdf. (and others) PMID: 9351880 Understanding the molecular basis of adverse effects of bisphosphonate drugs in the treatment of bone diseases MJ Rogers & K Thompson University of Aberdeen, Aberdeen, United Kingdom. Bisphosphonates are powerful inhibitors of bone resorption and have become blockbuster drugs in the treatment of metabolic bone diseases. Enormous progress has been made over the last few years in understanding exactly how bisphosphonate drugs act at the molecular level. After targeting bone and selective internalisation by osteoclasts, nitrogen-containing bisphosphonates potently inhibit FPP synthase. Inhibition of this enzyme disrupts the flux through the mevalonate pathway, the metabolic route required for the intracellular biosynthesis of the isoprenoid lipids that are required for the carboxy-terminal modification (prenylation) of small GTP-binding proteins such as Ras, Rho, Rac and Rabs. This modification is essential for the correct localisation of small GTPases to cell membranes. Prenylated small GTPases act as molecular switches, playing key roles in membrane ruffling, trafficking of vesicles, cytoskeletal organisation and cell survival. Inhibition of FPP synthase by bisphosphonates causes loss of synthesis of FPP and its metabolite GGPP, thereby preventing the prenylation of small GTPases. This results in the accumulation of the unprenylated forms of the proteins, thus disrupting osteoclast function and causing osteoclast apoptosis. The most significant adverse effect of intravenous bisphosphonate therapy is a ‘flu-like acute-phase reaction. We have recently demonstrated that this effect appears to be due to inhibition of FPP synthase in peripheral blood mononuclear cells, which causes an accumulation of the upstream isoprenoid lipid metabolites IPP and DMAPP. The latter are known to stimulate the Vgamma9Vdelta2 subset of gamma,delta-T cells, causing the release of TNFalpha and IFNgamma. This likely induces release of IL6 and C reactive protein and causes the rapid onset of ‘flu-like symptoms. Hence, the ability of nitrogen-containing bisphosphonates to inhibit the mevalonate pathway explains their well-known, potent inhibitory effects on osteoclasts as well as their transient, adverse effects that have been described clinically. Endocrine Abstracts (2005) 10 S37 www.endocrine-abstracts.org/ea/0010/ea0010s37.htm (35) The hormone, leptin, also regulates cholesterol: Within the liver, leptin treatment reduced the activity of 3-hydroxy-3-methylglutaryl-CoA reductase, but it did not change activities of cholesterol 7 -hydroxylase or acyl-CoA:cholesterol acyltransferase. These data suggest that leptin regulates biliary lipid metabolism to promote efficient elimination of excess cholesterol stored in adipose tissue. www.jbc.org/cgi/content/full/277/37/34117 Fat Hormone Tied to Multiple Sclerosis Italian Study: Blocking the Hormone Leptin Curbed Similar Disease in Mice Jan. 12, 2006 -- Blocking the hormone leptin may help prevent or slow multiple sclerosis (MS). (36) FcRn ameliorates murine Lyme arthritis by preventing the degradation of protective borreliacidal antibodies. PMID: 16415101 FcRn is a PROTECTIVE protein that transports IgG across the placenta to a fetus and saves IgG from degration in an adult. (IgA is secreted by mom’s colostrum.) It takes 2 FcRn molecules to transport one IgG molecule. IgG is “recycled” or is suppose to be. FcRn binds IgG at an acidic side and releases it at the basic side. IgG is the most abundant type of antibody we have. FcRn transports IgG in both directions across the epithelial cell barrier. The epithelial barrier is protective. However, some proteins, such as bacterial toxins, are able to breech this barrier and cause disease. If the transport protein, FcRn, is not bound to the antibody, IgG, it (IgG) is degraded. Individuals who do not have functional FcRn have an over-catabolism of IgG, leading to a much shorter lifespan for the antibody. Some, but very, very few people lack FcRn. These people are usually very vunerable to infections. FcRn also protects albumin (protein) from degradation. If we had failed to evolve an FcRn, we would require 2 livers the size of our existing liver to keep our albumin concentration normal, and we would need to biosynthesize four times more IgG than we do. Thus it is likely that the overabundance of IgG and “damaged” IgG (as seen in Lupus) may be due to too much (or not enough?) FcRn being produced. But why might this happen? Well…there is another protein…a calcium sensing protein called calmodulin which binds to FcRn in a calcium dependent and reversible fashion. Magnesium OR calcium can bind to calmodulin, but what happens when calcium binds is entirely different than what happens when magnesium binds to this protein. Magnesium increases the thermodynamic stability of calmodulin. It appears calcium and magnesium compete for the same sites. If Mg levels have dropped and if calcium levels have risen, it would appear that the calcium sensing protein, calmodulin, might bind and “inactivate” the protective FcRn protein and thus impact the circulating IgG antibodies. Don’t forget…TNF alpha’s jobs, one of them, is to rid the body of damaged (fab portion) antibodies. It takes Mg AND Ca to make healthy antibodies. www.bio.davidson.edu/Courses/Immunology/Students/Spring2003/Leese/First%20Page.html www.its.caltech.edu/~bjorker/Protocols/FcRn_sorting.pdf. www.its.caltech.edu/~bjorker/Protocols/Anti-FcRn_mAb_purification.pdf. www.jci.org/cgi/content/full/115/12/3440 www.everything2.com/index.pl?node_id=1689937 64.233.179.104/search?q=cache:87FSIC54ZoMJ:www.chnola-research.org/faculty/bdickinson/index.htm+FcRn+&hl=en www.pedresearch.org/cgi/content/abstract/53/2/295 ajpgi.physiology.org/cgi/content/abstract/290/2/G352 www.andersonlab.com/research.htm www.lupusresearch.org/lru_sum_04.html www.pubmedcentral.nih.gov/articlerender.fcgi?artid=125858 www.medschool.lsuhsc.edu/Pediatrics/faculty_detail.asp?id=1185 PMID: 11206069 PMID: 3651401 Valletta’s patent has merit. Lyme patients have reported several alternative treatments that seem to help. These include ozone or far infrared saunas (nitric oxide and acetylcholine reasons) and Rife or "approved" Ondamed therapy. Others have tried using high doses of Benicar or a Na-Vitamin C protocol. These are not without serious risks and should only be done with a doctor’s knowledge. Be sure to tell your doctor all the supplements/treatments you are taking/doing or thinking of taking/doing! When the lyme pathogen is destroyed, toxins are released and one experiences a “herx” or an increase in symptoms due to the acidic condition. It is my personal opinion that restoring Mg levels, following the guidelines in Dr. Valletta’s U.S. patent titled: Magnesium for Autoimmune would likely be the safest route to go. But TIMING (not necessarily huge doses) of the RIGHT nutrients to restore the balance is critical. There are many other things that will help on the journey to wellness. These include eating only healthy foods and drinking only healthy beverages – primarily good water. Nothing artificial. Cut back on sugar. Complex carbs are okay and needed. Stevia or Xylitol can substitute for sugar safely. Take probiotics every day with a full glass of water one hour before a meal. Take walks if possible every day for at least 20 minutes. Watch funny movies. Listen to healing music or your favorite upbeat music. Keep learning, keep reading…exercise your mind. Pray and don’t hesitate to ask for the prayers from others. Believe you are getting better. BELIEVE. The mind is very, very powerful. [ 19. February 2006, 10:57 AM: Message edited by: Marnie ] -------------------------------------------------------------------------------- Posted by lymeinhell (Member # 4622) on 02 December, 2005 04:55 PM : Up to the top!!! Read up - MAGNESIUM is so crucial to your getting well. Thanks for bringing this up again Marnie! -------------------------------------------------------------------------------- Posted by Marnie (Member # 773) on 09 January, 2006 04:43 AM : Recent research added. See #29. -------------------------------------------------------------------------------- Posted by johnnyb (Member # 7645) on 09 January, 2006 01:37 PM : Viva Magnesium!!! -------------------------------------------------------------------------------- Posted by treepatrol (Member # 4117) on 26 January, 2006 10:22 AM : Valletta’s patent has merit. Lyme patients have reported several alternative treatments that seem to help. These include ozone or far infrared saunas (nitric oxide and acetylcholine reasons) and Rife or "approved" Ondamed therapy. Others have tried using high doses of Benicar or a Na-Vitamin C protocol. These are not without serious risks and should only be done with a doctor’s knowledge. Be sure to tell your doctor all the supplements/treatments you are taking/doing or thinking of taking/doing! When the lyme pathogen is destroyed, toxins are released and one experiences a “herx” or an increase in symptoms due to the acidic condition. It is my personal opinion that restoring Mg levels, following the guidelines in Dr. Valletta’s U.S. patent titled: Magnesium for Autoimmune would likely be the safest route to go. But TIMING (not necessarily huge doses) of the RIGHT nutrients to restore the balance is critical. There are many other things that will help on the journey to wellness. These include eating only healthy foods and drinking only healthy beverages – primarily good water. Nothing artificial. Cut back on sugar. Complex carbs are okay and needed. Stevia or Xylitol can substitute for sugar safely. Take probiotics every day with a full glass of water one hour before a meal. Take walks if possible every day for at least 20 minutes. Watch funny movies. Listen to healing music or your favorite upbeat music. Keep learning, keep reading…exercise your mind. Pray and don’t hesitate to ask for the prayers from others. Believe you are getting better. BELIEVE. The mind is very, very powerful. United States Patent: 6,248,368,Inventors: Valletta; Giampiero (No. 188, Via Campidoglio, 03024 Ceprano {FR}, IT)
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Post by questionhair on Sept 14, 2006 13:39:55 GMT -5
THE PATENT: ========================
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Title: Use of magnesium based products for the treatment or prophylaxis of autoimmune diseases
United States Patent: 6,248,368
Inventors: Valletta; Giampiero (No. 188, Via Campidoglio, 03024 Ceprano (FR), IT) Appl. No.: 737743
Filed: November 21, 1996 PCT Filed: May 24, 1995
PCT NO: PCT/IT95/00089 371 Date: November 21, 1996
102(e) Date: November 21, 1996 PCT PUB.NO.: WO95/31991
PCT PUB. Date: November 30, 1995 Foreign Application Priority Data: May 25, 1994[IT] (RM94A0328)
Abstract
Pharmaceutically acceptable compositions suitable for releasing magnesium ions to an organism, such as organic or inorganic magnesium salts or complexes thereof, are used to prevent and to treat neoplastic and autoimmune diseases, whose origin can be attributed to magnesium depletion. For the new therapeutic indications the magnesium based product, preferably magnesium pyrophosphate, is usually administered orally or parenterally, preferably in association with vitamin B6.
Description of the Invention
SPECIFICATION
This invention relates to the use of magnesium containing products for the therapy and the prophylaxis of neoplastic and autoimmune diseases. More specifically, this invention relates to the use of magnesium, in the form of magnesium salts or complexes, or in any other form suitable for releasing Mg++ ions, for the production of drugs to be administered against neoplastic or autoimmune diseases, both for prophylaxis and for therapy purposes.
It is known that magnesium is a natural element widely diffused in living organisms, specially in mammals, wherein the largest concentration thereof occurs in bones. In humans, about 60% of the total amount of magnesium is stored in the bone tissues, about 34% in the soft tissues and about 5% in the intercellular spaces. It is also well known that magnesium, being a normal component of the blood plasma and a calcium antagonist, takes part in the muscle contraction mechanism and is vital for the action of a number of enzymes.
The daily magnesium requirement for humans ranges from 5 to 10 mg/per kg of body weight, and is normally supplied through the food, particularly vegetables. A magnesium deficiency in a living organism could be associated to abnormal muscle excitability as well as convulsions. This can occur in babies from birth, when the mother was already depleted of her own magnesium reserves, or when the baby is poorly supplied with magnesium, and/or undergoes high magnesium losses from his or her organism. When encountered in an adolescent, adult or aged person, a magnesium deficiency can be ascribed to generally stressing conditions, chronic intoxication or disease, to misabsorption, to alcohol or drugs abuse, as well as to hormone pathologies that cause magnesium losses for long time periods. More specifically, a magnesium deficiency referable to a poor supply can be due, e.g., to growth, pregnancy, breast feeding, anorexia, vomiting, overload of calcium, of vitamin D, of phosphorus, of alkalizing products, or to excessive intake of alimentary fibre, to low calorie diets, to alcoholism, etc. A magnesium deficiency referable to defects in magnesium metabolism can be due, e.g., to stress or neurosis, to nervous disorders or to endocrine-metabolic disorders (J. Durlach, "II magnesio nella pratica clinica", p. 118 and foll., IPSA, Palermo (1988)).
A magnesium deficiency or excess in an organism cannot be quantified as an absolute value, as the magnesium level in the blood is not related with the presence thereof in the deposit sites mentioned above. Generally speaking, the means for detecting the magnesium body contents include the detection of blood levels of magnesium, in the patient's plasma or in the serum (whose anomalies generally indicate a disorder in magnesium metabolism and are, normally, the starting point for a set of further specific tests); the detection of magnesium levels in the urine (which gives a measure of the elimination of magnesium via urine, and is normally associated with protein intake, being the Mg/urea ratio in the urine quite constant); the detection of magnesium levels in the spinal fluid; the detection of erythrocytic magnesium (which shows the amount of Mg contained in the bone marrow when erythropoiesis occurs and allows, therefore, an indirect medullary exploration as concerns magnesium--it is to be noted, however, that the erythrocytic magnesium level is a function of the erythrocyte age and, accordingly, a quick erythrocyte renewal is associated with an erythtocytic magnesium increase, without any reference to any magnesium excess); the detection of lymphocytic magnesium; nuclear magnetic resonance with 25 Mg (which evidences any modifications in the subcellular distribution of magnesium and in the different chemical-physical structures); and, finally, the detection of magnesium contents in the patient's bones and muscles.
According to the current medical opinion, the administration of magnesium would promote the growth of established solid tumours and generally the worsening of autoimmune diseases (see, e.g., J. Durlach, p. 215-216, cited above). Such opinion is based on the finding that erythrocytic magnesium increases when a tumour is under development or when a chronic disease, such as for example hepatic cirrhosis, shows a malignant degeneration, or when an autoimmune disease shows a recrudescence. Furthermore, the erythrocytic magnesium level would decrease when these diseases are under remission.
Specifically, at the onset of a tumoral or of an autoimmune disease a magnesium depletion takes place throughout the organism, together with a simultaneous transfer of said element from the bone marrow to the newly formed erythrocytes, and with a massive transfer of said element, carried out by the erythrocytes, to the tumoral areas or to the areas affected by the autoimmune disease. In all cases, a magnesium increase in the blood is detected. In view of that, according to the current medical opinion magnesium is the "fuel" used by the tumour or autoimmune disease to progress.
Accordingly, the conventional therapies use immunosupressants to treat autoimmune diseases and antineoplastic chemotherapy agents to treat tumoral diseases, i.e. they use drugs aimed at reducing the cell mitotic activity in so far as it is more accelerated. These drugs actually slow down the cell metabolism (thus acting more on the affected cells than on the healthy cells), but they also cause a drastic magnesium depletion throughout the organism.
The theory according to which a solid tumoral disease can be made to regress by depleting the magnesium contents in an organism was confirmed by the findings of Parson and colleagues in 1974 (F. M. Parson et al., "Regression of malignant tumours in magnesium and potassium depletion induced by diet and haemodialysis", The Lancet, 16.02.1974), who obtained a partial regression of neoplastic lesions in some "end-stage" patients by inducing a forced magnesium depletion throughout the organism. Said depletion had been obtained by combining an almost magnesium free diet with a haemodialysis procedure, through which a high amount of magnesium was removed daily from the patient.
The validity of this therapeutic approach seems not to have been confirmed after such first attempts; however, up to now the leading medical opinion considers the admistration of magnesium as a harmful measure in respect of most neoplastic diseases and of autoimmune diseases.
According to the theory underlying the present invention, on the contrary, it has now been found that, both in man and in animals, a magnesium deficiency can actually be the origin of pathologies which are ascribable both to an excess and to a deficiency of the immune response. As it is well known, in the case of an excess of immune response, the organism shows a reactivity alteration which results in its generating autoimmune antibodies (i.e., antibodies against some components of the same generating organism), thus developing autoimmune diseases. In the case of a deficiency of said response, on the other hand, tumors or diseases from viral, bacterial, parasitic or fungal agents, that the organism is unable to defeat, could arise.
According to this invention, whether an organism depleted of magnesium shows the first or the second reaction mentioned above depends upon the variability of the genome of any single individual. Said variability makes the immune system behave hypo- or hyper-reactively according to the individual diathesis. In both cases, however, the occurrence or progression of a disease, which is the result of an inadequate immune response, has as its starting cause a magnesium deficiency.
By taking specifically into account the neoplastic diseases, it is well known that a human or animal organism generates daily about twenty tumoral cells as average. Such cells are normally recognized by the immune system as a foreign substance, on the basis of the detection of their altered gene sequences, and are then removed. When this does not occur and the immune mechanism is slowed down or made ineffective because of a magnesium deficiency, the malignant cells (poorly differentiated or even not differentiated at all, but very aggressive and not mutually bound, due to the absence of an intercellular bonding substance) develop, then overwhelming the ability of the hosting organism, the survival of which depends upon maintaining a very high differentiation level of the cell patrimony.
As to the autoimmune diseases, the difference with respect to tumoral diseases consists in the fact that in this case (which occurs in alternative to the case of tumoral diseases owing to the individual genome difference, as pointed out above) the immune system shows, instead of being hypoergic, a form of hyperactivity not intended at defending the organism, but directed against some components of the same, recognized as foreign substances. Unavoidably, this mechanism leads to a form of self-cannibalism.
In all cases, a possible latency of a disease induced by a magnesium deficiency depends mainly from the quality of the constitutional or acquired homeostatic mechanisms, of a general nature or specific for the magnesium regulation. Said quality vary from one individual to another, and it is obvious that the individual tolerance of a chronic magnesium depletion is different from one case to another, according to the quality of the magnesium homeostasis. Anyway, it is a general opinion that decompensation factors are required to cause the appearance of a symptomatology.
In view of the foregoing, according to this invention there is proposed to use magnesium, or preferably any physiologically acceptable source of Mg++ ion, to treat solid tumoral diseases, as well as to prevent and treat autoimmune diseases.
Magnesium-containing products in the form of organic or inorganic salts, or in the form of magnesium ion complexes, are already used in therapy, mainly as antacids, laxative and purgative preparations, but also as metabolism regulators, anticonvulsants and sedatives. Obviously, it should be noted that not in all of the active substances containing magnesium ions the latter perform a true therapeutic function. In the case of magnesium sulfate, for instance, it is ackowledged that the laxative action is rather due to the osmotic conditions of the solutions employed and to the typical function of the sulfate anion, than to the properties of the magnesium ion. Therefore, the new medical indications according to this invention can be put into practice by using any magnesium compound which is able to supply the organism with Mg++ ions in absorbable form, and which does not show further therapeutic activities incompatible with the activity considered by this invention.
Thus, the present invention specifically provides the use of a pharmaceutically acceptable magnesium salt or complex in the manufacture of a medicament for the therapy of solid neoplastic diseases and for the therapy and/or the prophylaxis of autoimmune diseases.
The pathologies that, according to the invention, are considered to be new indications of the magnesium therapy are, in the field of the neoplastic diseases the solid neoplasies (i.e., organ neoplasies) and, in the field of the autoimmune diseases, any so properly called disease, as well as any diseases showing an autoimmune mechanism. The so-called autoimmune diseases comprise rheumatoid arthritis, local and systemic scleroderma, systemic lupus erythematosus, discoid lupus erythematosus and cutaneous lupus, dermatomyositis and polymyositis, Sjogren's syndrome, nodular panarteritis, autoimmune enteropathy, proliferative glomerulonephritis, active chronic hepatitis and the polyglandular deficiency autoimmune syndrome type 1 and 2. The diseases that involve anyhow an autoimmune mechanism comprise multiple sclerosis, pemphigus vulgaris and pemphigoids, psoriasis and parapsoriasis, intestine inflammatory diseases such as the ulcerative colitis and the Chron's disease, vitiligo and sarcoidosis.
The conventional therapies for the above diseases widely vary, ranging from surgery to irradiation and physiotherapic treatments, and in most cases, to chemotherapy, using a number of different active substances, among which cortisone, immunosuppressants, interferone and cortico-steroids. On the contrary, according to this invention, all of the above pathologies are to be connected with a more or less severe magnesium deficiency, which results in either an unsuitably weak or in an excessively strong immune response. Thus, a proper magnesium therapy, optionally but not necessarily associated with conventional treatments, can bring the organism to restore the correct functions of the immune system and, consequently, to defeat the above pathologies.
As to the mechanism of action, it is believed that magnesium therapy, by restoring the optimal magnesium levels, leads the immune system to increase the production of the Th1 sub-population of T-helper lymphocytes, thus increasing the cell-mediated immune system response. Actually, it is well known that Th1 lymphocytes mainly secrete interleukin 2 and gamma interferon, and that these cytokines stimulate a cell-mediated response, that removes the infected elements from the organism (Mossmann and Coffmann, DNAX Research Institute, Palo Alto, Calif.).
The magnesium based compound to be used in the therapy according to this invention can be in the form of a stoichiometric salt or in the form of a magnesium ion complex, i.e. associated agents which enhance the absorption when orally administered. In turn, the salt can be an organic salt, such as magnesium lactate, aspartate or acetate, or an inorganic salt, such as magnesium pyrophosphate. Magnesium pyrophosphate, also known as magnesium pidolate, is the preferred compound according to this invention, and is already used as a nervous system suppressant and against hyperexcitability, muscle contractions and cramps.
The administration of magnesium based products in the therapy of neoplastic or autoimmune diseases according to this invention can be made both orally and parenterally and, in the latter case, both through intramuscular and intravenous injections. In some cases a dermal or mucosal administration is also advantageous, as is shown in the following description.
As previously indicated, the magnesium can be used both alone and associated with the medicaments conventionally used against the concerned diseases. In the latter case, the magnesium treatment could be carried out before, during or after the conventional therapy, in order to restore a normal immune response.
Taking into account that the average magnesium requirement in an adult is 6 mg per kg of body weight per day, and that such requirement strongly increases, up to double this amount, during the catabolism stages (e.g., diseases), the therapeutic dose for oral administration in such cases has to range from 2 to 12 mg of magnesium per kg of body weight daily, preferably from 8 to 10 mg per kg of body weight daily. When using magnesium pyrophosphate, this amount is equivalent to 25-148 mg/kg body weight daily, preferably 95-123 mg/kg body weight daily. However, the optimal amount is about 9 mg of Mg++ per kg of body weight daily, i.e. 111 mg of magnesium pyrophosphate/kg body weight daily.
When oral administration is poorly tolerated, resulting, e.g., in diarrhoea, or when misabsorption, vomiting and coma occur, or the patient is under aesthesia, etc., parenteral administration is employed, with magnesium doses ranging from 2 to 30 mg/kg body weight daily, corresponding to 25-368 mg/kg body weight daily of magnesium pyrophosphate. In most cases magnesium amounts ranging from 8 to 10 mg/kg body weight daily (i.e. 98-123 mg/kg body weight daily of magnesium pyrophosphate) are sufficient.
The same amounts of orally or parenterally administered magnesium are generally effective for newborns, babies, children and youngsters. Anyhow, the dosage depends not only upon the body weight, but also upon the patient's age and tolerance and upon stage of the disease. The highest amounts will be administered in the most severe cases of the above diseases (e.g., tumors with local or replicated metastases) by continuous infusion throughout 24 hours. The daily magnesium dose is to be diluted in a phleboclysis so as to supply the organism with no more than 80-100 mg of magnesium per hour.
It should also be considered that both parenteral and oral magnesium therapy in pharmacodynamic doses are to be associated with monitoring of the patient's plasma-magnesium level, pulsation, arterial pressure, bone-tendinous reflexes, electrocardiogram and respiration rhythm.
As an alternative to the intravenous administration the intramuscular ruote can be employed, by injecting 2-4 mg of Mg++ /kg body weight daily (equivalent to 25-45 mg of magnesium pyrophosphate/kg body weight daily) divided into one or two administrations, until the oral or intravenous route can be employed.
In the frame of the magnesium therapy as suggested by this invention, care should be taken to prevent any magnesium excess, the consequences of which are as follows:
when the blood magnesium levels are below 1.5 mmol/l any magnesium excess is masked;
for blood magnesium levels over 1.5 mmol/l hypotension, transient tachycardia followed by bradycardia, as well as nausea, vomiting and headache are possible;
blood magnesium levels over 2 mmol/l result in reduced tendon reflex, muscle hypotony and sleepiness, oliguresis, extension of the sections P-R and Q-T of the electrocardiogram;
when the blood magnesium levels are over 4 mmol/l, a total loss of tendon reflex is shown, followed by myoparalysis, specially respiratory paralysis, followed by hypothermic coma and cardiac arrest.
It should be noted that a magnesium excess, if any, can be treated with intravenous administration of calcium, osmotic diuresis, administration of anticholinesterases, analeptics and glycoside cardiotonics and, in the most severe cases, with artificial respiration and dialysis.
The contraindications in respect of an oral or parenteral magnesium therapy comprise the simultaneous administration of drugs having a curarizing effect on the motor plate (gentamicin, streptomycin, amikacin, tobramycin among the antibiotics; quinidine-based drugs among the antiarrythmics; hydantoins among the antiepilectics; diazepam and phenothiazines, etc. among the sedatives); of high doses of hypnotics and barbiturates, that depress the respiration center; of corticotherapy agents and betamimetics, that promote lung oedema and myocardium ischemia. A transitory contraindication can be an infection of the urinary tract, that could cause phosphorous-ammonium-magnesium salts to precipitate; accordingly, any urinary tract infection must be treated before starting a magnesium treatment.
The magnesium therapy according to this invention can also be carried out through cutaneous or mucosal administrations, as previously indicated, by means of baths, irrigations, ointments ant the like, in order to treat the local dermal or mucosal symptoms showed in the course of the concerned diseases. The Mg++ concentration and the administration frequency differ according to the pathology type and the affected areas.
It is convenient to associate the magnesium therapy with the administration of some magnesium fixing substances, such as vitamin B6, in order to improve the magnesium transfer, to increase the plasma levels of magnesium and to reduce the magnesium removal via urine. Preferably, vitamin B6 is used with this aim, in a ratio with the Mg++ ions in the range from 2:1 to 3:1, the optimal ratio being 2.5:1.
A reduced magnesium removal via urine can also be obtained through an antistress treatment (such as an hygienic life behaviour or a soft sedative treatment), or by avoiding excessive protein ingestion, or by using potassium retaining diuretics, such as amiloride or spironolactone. However, the use of potassium retaining diuretics is limited to the cases wherein the magnesium removal via urine is too high both as an absolute value and in respect of the urea contents in the urine.
A magnesium therapy carried out according to this invention leads to recovery of the previously indicated diseases within a time interval from three to twelve months, it being understood that "recovery" means the lesions disappearance and/or a reduction to negative values of the activity indexes of the disease, associated with a stop of the disease progression when such tissue lesions are produced that no "restitutio ad integrum" can take place (such as, e.g., in cases of articular ankylosis, nerve lesions, fibrotic effects on muscles, etc.).
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Post by questionhair on Sept 14, 2006 13:40:55 GMT -5
(continued)
When the complete clinical and analytical recovery has been obtained, the magnesium therapy can be discontinued, although it is convenient to repeat it in physiologic amounts each year, from March to June and from September to December, preferably with 5-6 mg of Mg++ /kg body weight daily, equivalent to 67-71 mg of magnesium pyrophosphate/kg body weight, orally administered. Also in this case it is convenient to associate the magnesium treatment with a vitamin B6 administration at a ratio vitamin B6 /Mg++ equivalent to 2.5:1. This therapy scheme with physiologic amounts is suggested to any healthy person, who wants to prevent any occurrence of the previously mentioned diseases.
The studies carried out in connection with this invention and the related clinical experiments, examples of which will be given hereafter, allow to formulate some hypoteses on the role of magnesium in neoplastic and autoimmune diseases. Such hypotheses are summarized below.
A magnesium deficiency in an organism causes a reduced blood level of magnesium in the intercellular space, and a parallel lowering of such element in the cells, which results in a permeability increase of the cell membranes. The consequent depolarization causes a reduction of the intracellular potassium and a related increase of the intracellular calcium. Therefore, such ion changements cause a reduced blood-calcium level and an increased blood-potassium level. When the magnesium deficiency is protracted, the intracellular calcium excess could cause insoluble crystals of calcium, phosphorus and magnesium to precipitate within the cells; these salts, although being not physiologically significant, in the event of a severe and prolonged magnesium deficiency increase the intracellular phosphorous contents, as well as, paradoxally, the intracellular magnesium contents. The temporary organism response observed by Parson et al. as an effect of the heavy magnesium deficiency induced in patients with end-stage cancer, as reported above, can be ascribed to such increase of the intracellular magnesium.
Similarly, the drastic magnesium depletion in an organism, as induced by the immunosupressants, causes an intracellular magnesium increase according to the pattern outlined above, and causes the same effects.
On the contrary, according to the findings of this invention, at the onset of a neoplastic or of an autoimmune disease the even scarce magnesium reserves in an organism are deemed to be used at an accelerate rhythm and in an increased amount just to fight the disease. As time elapses, the magnesium stocks of the organism, when not adequately restored, are depleted; and magnesium is drawn from any site from where it is available, including, when the disease continues, the main reserves, i.e. the bone tissues, until these reserves exhaust.
In this connection, it should be noted that it is right in the in the bone tissues that the the erythrocytes are synthesized, and that said erythrocytes will proceed, loaded with magnesium, towards the tumor sites of the affected areas, to counteract the disease development. When no magnesium therapy is carried out, the magnesium reserves shall exhaust, thereby weakening the immune system, particularly the cell-mediated section thereof.
Considering the large new-formed vascular network around a solid malignant tumor, which is considered by the current medical opinion as a penetration factor induced by the neoplasm for its own advantage, in order to improve and accelerate its infiltration into the healthy tissue, it is believed, on the contrary, that such network is a defence system of the organism against the neoplasm, aiming at allowing the suitable immuno-competent agents to reach the pathologic areas more quickly and in a higher amount, to fight the tumor most effectively.
Claim 1 of 25 Claims
What is claimed is:
1. A method of treating autoimmune diseases sensitive to treatment with magnesium in humans and animals, which method comprises administering to a host in need thereof a composition consisting essentially of an effective amount of a pharmaceutically acceptable magnesium salt or complex.
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