Overview of Mercury Toxicity - Medical Books


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Overview of Mercury Toxicity - Medical Books

  1. 1. My Dentist Hurt My Feelings (for Several Decades) a small treatise on the nasty psychological side effects from the mercury vapor emitted from “silver” dental fillings by Stevenson Munro a Fifth Business Production
  2. 2. Nineteen fillings by the age of 16. All my life I’ve struggled with being tired, anxious, moody, spacey, forgetful, reclusive and uncoordinated.
  3. 3. German Chemist Alfred Stock’s First-Hand Account of Mercury Vapor Poisoning. P. Stortebecker, MD, PhD, Mercury Poisoning from Dental Amalgam – A Hazard to the Human Brain , Bio-Probe, Orlando, FL, 1986 First Stage : Predominantly psychic symptoms. Fatigue. Diminished working capacity. Irritability. Slight swelling of mucous membranes in upper nasal region. Second Stage : Extreme Fatigue. Lack of concentration. Impaired memory for names, numbers, etc. Irritability and moodiness. Sensation of a “sheer stupidity.” Nasal obstruction and dryness, a “stuffed nose”. Nasal discharge, viscous, sticky, sometimes bloody. Ringing in the ears. Hearing impairment. Headache, often frontal. Stomatitis, bleeding gums on tooth-brushing. Irregular heart activity. Sometimes diarrhea. Frequent urination. Slight tremor. Third Stage : Troublesome headache. Dizziness. Vertigo. Tremor. Mental incapacity. Despondency and depression. Back pain. Painful and difficult urination. Colitis with diarrhea. Nasal catarrh, with bloody nasal crusts. Loss of smell. Stomatitis, bleeding gums. Paradentosis, loose teeth. Increased salivation. Pharyngitis and laryngitis, etc. Stock’s worst complaints were his EXTREME FATIGUE and lack of working capacity. I personally experienced all of Alfred Stock's reported symptoms.
  4. 4. Metallic mercury has been known since ancient times, as has its capacity for producing illness. The metal is appreciably volatile, so that toxicity results from inhalation exposure of the vapor. Often, the earliest signs of neurotoxicity are personality changes. At first subtle differences in mood and behavior may be noted only by family members or close friends or associates of the affected individual. As exposure continues, behavior may become increasingly neurotic or even psychotic. Pathological shyness or reclusiveness is a characteristic sign, sometimes alternating with exaggerated irritability. Mild sensory loss may appear early, with tingling in toes, fingers, or around the lips. A mild tremor develops, which becomes more severe as exposure continues. Twitching eyelids may appear first, followed by a tremor of the hands. Fine motor control becomes difficult; as evidenced by noticeable changes in handwriting or drawing.   Many of these signs and symptoms appeared in hatters using volatile mercury salts for treating felt. Hence the "mad hatter" of Alice in Wonderland may have basis in fact. Reeves, A.L.; Toxicology: Principles and Practice , Vol. 1, 1981, p. 127 Modern toxicology book confirms Stock’s symptom profile for mercury vapor poisoning
  5. 5. Standard medical reference confirms toxicity Cecil Textbook of Medicine, 21 st ed., Vol. 1, p. 72 Elemental mercury is a liquid at environmental temperatures but vaporizes with agitation as well as gently heating. Bulk mercury is used in dental amalgams. . . Elemental mercury is readily absorbed from the alveoli; subsequently it can enter the brain. With mild exposure, the manifestations are likely to be subtle and diagnosis is difficult. Insomnia, nervousness, mild tremor, impaired judgment and coordination, decreased mental efficiency, emotional lability, headache, fatigue, loss of sexual drive, and depression are early manifestations and are often mistakenly ascribed to psychogenic causes. Abdominal cramps, dermatitis, and diarrhea may also occur, and the victim may complain of a metallic taste. As the poisoning becomes more severe, persistent involuntary tremors of the extremities are noted. Thereafter, other signs of mercury poisoning may appear, including amblyopia, polyneuropathy, erythroderma, acrodynia, joint pains, swollen gums with a blue line around the teeth, sialorrhea, and paresthesias. The major manifestation of chronic mercury vapor exposure may be kidney damage, including the nephrotic syndrome. Because of the body’s metabolism of mercury, blood and urine levels may be unreliable and clear evidence of poisoning may be documented only after administering drugs that augment mercury excretion in the urine. In most cases, improvement occurs after removal from exposure or treatment with appropriate chelating agents.
  6. 6. Not a fluke: another standard medical reference says the same thing . . . Harrison’s Principles of Internal Medicine, 15 th ed., Vol. 2, p. 2593 CLINICAL TOXICOLOGY Inhalation of metallic mercury vapor is the form of mercury exposure that has been best studied in terms of toxicity. High levels of exposure are most likely in an occupational setting in which mercury vapors are generated by heat-induced volatilization of metallic mercury. Cough, dyspnea, and tightness or burning pain in the chest are common symptoms that may be accompanied by diffuse infiltrates or a pneumonitis-like appearance on chest x-ray. Respiratory distress, pulmonary edema, lobar pneumonia, fibrosis, and desquamation of the bronchiolar epithelium can occur in relatively severe cases and have sometimes lead to death. Acute inhalation of mercury vapor can also cause neurologic toxicity manifested by tremors (beginning in the hands), emotional lability, headaches, and polyneuropathy. Chronic exposure to metallic mercury produces a characteristic intention tremor and mercurial erethism , a constellation of findings including excitability, memory loss, insomnia, timidity, and sometimes delirium that was described in workers with occupational exposure in the felt-hat industry – hence the expression “mad as a hatter.” Dentists with occupational exposure to mercury score below normal on neurobehavioral tests of motor speed, visual scanning, verbal and visual memory, and visuomotor coordination. Low-level exposure from dental amalgams may also be associated with adverse immunological reactions with certain major human leukocyte antigen genotypes; further research is needed in this area.
  7. 7. In disbelief, I found the story repeated in numerous authoritative medical reference books and journal articles: <ul><li>Tietz Textbook of Clinical Chemistry , 3 rd ed., pp. 992-998
  8. 8. Poisoning: Toxicology, Symptoms, Treatments , 5 th ed., pp. 199-209
  9. 9. Clinical Management of Poisoning and Drug Overdose , 3 rd ed., pp. 750-756
  10. 10. Casarett and Doull’s Toxicology: The Basic Science of Poisons , 6 th ed., pp. 834-837
  11. 11. Gerstner and Huff, “The Clinical Toxicology of Mercury”in the Journal of Toxicology and Environmental Health 2:491-526, 1977
  12. 12. Verity & Sarafian (2000) Mercury and Mercury Compounds. In: Experimental and Clinical Neurotoxicology 2 nd ed. Spencer PS et al., ed. , Oxford University Press, New York / Oxford pp. 763-770, 2000
  13. 13. Kark RAP (1994) Clinical and neurochemical aspects of inorganic mercury intoxication. In: Investigations of the Nervous System. Vol. 64. DeWolfe FA ed. Handbook of Clinical Neurology. Vinken PJ, Bruyn GU eds. Elsevier/North Holland, Amsterdam pp. 367- 411 </li></ul>
  14. 14. “ There have been epidemics of mercury poisoning among wildlife and human populations in many countries. With very few exceptions and for numerous reasons, such outbreaks were misdiagnosed for months or even years . Reasons for these tragic delays included the insidious onset of the affliction, vagueness of early clinical signs, and the medical profession's unfamiliarity with the disease.” Hardman JG, Limbird LE, Eds., GOODMAN & GILMAN'S THE PHARMACOLOGICAL BASIS OF THERAPEUTICS , 10th ed., McGraw Hill (2001) So why didn’t any of my doctors ever tell me?
  15. 15. Hg0 poisoning is hard to detect, because the symptoms are so variable Continued exposure to moderately high concentrations of mercury vapor in air - which do not trigger the acute pulmonary syndrome - induces classical mercurialism, a chronic intoxication that displays clinical sequelae mainly arising from the central nervous system. Because of its ability to penetrate the blood-brain barrier, elemental mercury slowly accumulates in the most important human organ. Yet, the induced disease does not appear as a typical entity but as a wide spectrum of clinical pictures, ranging from almost imperceptible disturbance to complete incapacitation. Depending on mercury concentration, on length of exposure, and probably on individual sensitivity, manifestations of intoxication emerge insidiously; they gradually progress to various degrees of severity; and they create protean clinical pictures with broad spectrums of signs and symptoms. Gerstner and Huff, “The Clinical Toxicology of Mercury” Journal of Toxicology and Environmental Health 2:491-526, 1977
  16. 16. Affect. Mercurialism also manifests itself in an alteration of the emotional state. With an insidious onset, the mood generally swings toward the depressive side. Exposed persons experience feelings of fatigue and listlessness; they lose interest in their surroundings and in their own life; they withdraw more and more from social contacts; they become increasingly irritable and sensitive, reacting strongly to relatively innocent remarks uttered by family or friends; and they have a tendency for sweating and blushing. In this blushing - or reddening - the classical term &quot;erethism“ finds its origin. In very severe cases, the depression may reach suicidal proportions. Or the clinical picture may simulate manic-depressive psychosis with hallucinations and delusions. Mentality . Insidious in onset and difficult to recognize, a deterioration of intelligence gradually emerges during chronic exposure to elemental mercury. Previously bright persons become dull and slow in thinking. They suffer from a progressive decline affecting memory as well as the faculties for logical reasoning and concentration on particular problems. Hg0 poisoning induces a wide range of psychiatric disturbances Gerstner and Huff, “The Clinical Toxicology of Mercury” Journal of Toxicology and Environmental Health 2:491-526, 1977
  17. 17. Experts Agree: It’s an Intriguing Neurotoxin. Nothing else even comes close! “ Inhaled mercury vapor produces a range of fascinating and bizarre changes in human behavior from the grotesque to the extremely subtle. Modern psychological tests reveal subtle mood changes and less obvious personality changes. Erethism is a wide spectrum of psychological and personality disturbances. One end of the spectrum involves delirium, hallucinations, excessive shyness, and fits of rage. . . [while] irritability, insomnia, and lassitude may be the lower end of the erethism spectrum. . . No other metal can affect the central nervous system in this way. In fact, it is doubtful that any chemical, even hallucinogenic drugs, can compare with mercury vapor. It is a tantalizing problem to the neuroscientist. What a pity so little effort has been devoted to elucidating the physiological and biochemical mechanisms!” Clarkson, T.W. “Human Toxicology of Mercury” The Journal of Trace Elements in Experimental Medicine 11:303-317 (1998)
  18. 18. What is a safe level of vapor? The U.S. Environmental Protection Agency sets a non-occupational “reference air concentration”. In 1996, the RfC was: 0.300 ug Hg0/m3 The U.S. Agency for Toxic Substances and Disease Registry (ATSDR) publishes a “Minimal Risk Level” for non-occupational exposure. In 1999, the MRL for mercury vapor was set at: 0.200 ug Hg0/m3
  19. 19. So What’s in Our Mouths? Lichtenberg, H, “Mercury vapor in the oral cavity in relation to the number of amalgam fillings and chronic mercury poisoning” Journal of Orthomolecular Medicine 11:2 1996 pp. 87-94 Range: 3 ug – 195 ug
  20. 20. Oops Where’s the FDA? Dental amalgam has never been subjected to safety testing. It’s been “grandfathered in” as safe by the FDA. Where’s the Maine DEP and Department of Health? I have a little story . . . What other pre-Civil War medical devices would you like to be subjected to? The last Quacks: from “quacksilber”, quicksilver, the German word for mercury . . .
  21. 21. Like old folks in search of affordable prescription drugs, I went to Canada to search for accurate health information
  22. 22. So - I received 16 to 18 fillings too many before I could vote or die in war for my country
  23. 23. <ul><li>YOU FEEL LIKE SHIT BEFORE YOU SHAKE : In Fawer et al ., “safe levels” were based on forearm tremors. What about mood disturbances, shyness, irritability, attention and memory problems? Occupational studies show that these often come first. The question is: should we wait until Dad is trembling before we say there is a problem, or should we stop the exposure when he gets irritable as hell, shouts at the kids, has no friends, and sleeps on the sofa all the time?
  24. 24. A SAFE AMOUNT OF POISON ISN’T THE SAME AS A SAFE AMOUNT OF POISON WITH AN ANTIDOTE: 12 out of the 26 study participants were employed in chloralkali plants – thus, they were guaranteed a large margin of protection from mercury vapor exposure. Chlorine gas combines with mercury in the air and precipitates it to the ground. It also combines with mercury in the body, protecting the brain and heart from mercury vapor’s toxic effects. Dental amalgam bearers DON’T have this luxury. The vapor from their fillings goes straight into the blood stream and mercury collects at high levels in their brain.
  25. 25. SAFETY LEVELS SHOULD PROTECT THE MOST VULNERABLE: The 26 study participants were “self-selected” employees of mercury-using industries. That is, if they felt rotten in the presence of mercury vapor, then they could quit. Only the “mercury hardy” would stay employed, conceivably, to show up for the study. Amalgam wearers can’t take their fillings out when they feel bad -- they’re stuck with them for life. </li></ul>Even Canada's “safe exposures” are too much. The assumptions used (from Fawer et al., 1983) to determine “safe” levels of mercury vapor exposure are seriously flawed
  26. 26. In support of “you-feel-like-shit-before-you-shake” hypothesis: Exhibit A “ Personality changes are the most common findings in chronic mercurial poisoning. In mild cases these may occur with no other signs or symptoms apparent. The psychopathologic effects have been described as erethism, irritability, irascibility, critical excitability, fearfulness, restlessness, insomnia, inability to concentrate, melancholy, depression, shyness, timidity, moroseness, fatigue, weakness, and drowsiness. The person may appear indecisive and have memory deficit. Headache and digestive disturbances often are present.” Zenz C, Occupational Medicine, Chicago, Ill, 1975
  27. 27. Smith RG, Vorwald AJ, Patil LS, Mooney TF, Effects of exposure to mercury in the manufacture of chlorine, Am Ind Hyg Ass J 31 1970 687-700 Exhibit B: 642 workers in the chloralkali industry studied for one year <ul><li>Nervous symptoms increased in prevalence before objective tremors.
  28. 28. Like Fawer et al ., this study had a significant self-selection bias. More than 80% of the workers studied had worked in the mercury cell rooms for 2-14 years, while 85% of workers leaving the mercury cell rooms in the previous 10 years had done so voluntarily. </li></ul>
  29. 29. What of the chlorine gas “antidote”? The effect of chlorine on mercury vapor intoxication. Autoradiographic study Viola PL & Cassano GB Med Lavoro 59 1968 437-44 Sixteen Swiss Albino Mice -- 8 exposed to Hg0, and 8 exposed to Hg0 AND chlorine gas.
  30. 30. “ After about six weeks of exposure to mercury vapors the rats revealed hyper-excitement, sometimes followed by ataxia and tremor. The rats exposed to mercury and chlorine vapors showed mild dyspnea, cough and diarrhea in the second week. After eight weeks, ten out of forty rats of the first group died while four out of forty of the second group died.” 80 Wistar Rats Exposed: 40 to Hg0, and 40 to Hg0 + chlorine vapors The effect of chlorine on mercury vapor intoxication. Autoradiographic study Viola PL & Cassano GB Med Lavoro 59 1968 437-44 80 Wistar Rats Exposed: 40 to Hg0, and 40 to Hg0 + chlorine vapors
  31. 31. The Disturbing Conclusion “ The severe neurological symptoms presented by the rats exposed to mercury vapors only and the mild gastrointestinal disorders observed in the animals exposed to mercury and chlorine vapors indicated quite different intoxication pictures. The different type of poisoning . . . seems to be clearly explained by the higher mercury levels found in the brain, which were ten times higher than those observed in the nervous tissue of rats exposed to mercury and chlorine vapors. From the data reported in this paper we may conclude that chlorine vapors added to an atmosphere containing mercury vapors not only reduce mercury absorption [by 40%], but also determine a different distribution pattern of the metal in the body. The reason for this appears to be the transformation of mercury vapors into mercurous chloride. In fact, mercurous chloride passes the blood brain barrier in very small amounts, if at all, and does not concentrate in the heart muscle, as demonstrated after oral administration of HG203-Cl salt. A strikingly higher toxicity after exposure to an atmosphere containing only mercury vapors as compared to one with mercury and chlorine vapors should be emphasized.” The effect of chlorine on mercury vapor intoxication. Autoradiographic study Viola PL & Cassano GB Med Lavoro 59 1968 437-44
  32. 32. <ul><li>Alcohol Analogy is Apt – the mercury poisoned are like Chinese stuck in a town run by the Irish mob. All deals are sealed with drinks, and the drinks are not voluntary. You’d have a LOT of sick Chinese trying to get help at the hospital, and a lot of Irish nurses and doctors looking at them like they are crazy.
  33. 33. Wilson’s Disease (copper overload) and Hemochromatosis (iron overload) are good model diseases to understand mercury’s variable toxic effects
  34. 34. Mercury-resistant mammallian cells have been cloned that over-express intracellular levels of the antioxidant glutathione
  35. 35. Differences in ApoE proteins, glutathione protein synthesis and metallothioneins are all being reported by clinicians dealing with mercury-poisoned patients
  36. 36. Pink Disease – “acrodynia” – established two incontrovertible facts: </li></ul>1) health care providers can unwittingly poison large swaths of the population with mercury, and 2) the susceptibility to mercury poisoning is, indeed, HIGHLY variable. Some get poisoned by amounts that leave others unscathed. The successful termination of Pink Disease in the 1950’s, when mercury-containing infant medicines were voluntarily withdrawn from the marketplace by drug companies, SHOULD have been the death knell to mercury dental amalgams. Alas . . . Individual Sensitivity to Toxic Effects is Key
  37. 37. Pink Disease: the iatrogenic poisoning of babies with mercury-containing teething powders & worming medicines <ul><li>Dally, Ann, “The Rise and Fall of Pink Disease,” The Society for the Social History of Medicine, 10:2 (1997), 291-304
  38. 38. Acrodynia and mercury Warkany J & Hubbard DM J Pediatr 42 1953 365-86
  39. 39. Acrodynia - Postmortem of a disease Warkany J Am J Dis Child 112 1966 147-56
  40. 40. http://www.neonatology.org/pdf/pinkdisease.pdf
  41. 41. Pink Disease Support Group Mrs. Heather Thiele </li></ul><ul><ul><li>PO Box 134 Gilgandra NSW 2827 Email: hmthiele@hwy.com.au </li></ul></ul>For over a hundred years thousands of children were killed by accidental poisoning, and many more suffered in misery Warkany estimated that 1 in 500 exposed infants developed the disease. No epidemiological work was ever done. The disease disappeared after the mercury-containing medicines were withdrawn from the market. Provocatively, adult survivors of Pink Disease tend to have Asperger’s Syndrome.
  42. 42. Kark RAP (1994) Handbook of Clinical Neurology. Modern Allopathic Medicine says: Old Homeopathic Medicine says: Certain dentists are themselves aware of the popular dread of mercury and hence the false term of “Silver Filling” which is a deliberate swindle and a disgrace to the dental occupation. It is not claimed that mercury worn in the mouth is universally detrimental to health. My own experience, which includes hundreds of observations, leads to the conclusion that injurious effects are detected in only a small percent of those who wear red rubber and silver fillings. But the exceptions are frequent and the results are no doubt often disastrous. So disastrous, in fact, as to warrant the absolute and unqualified condemnation of the practice. Howard Drutcher, MD, Hahnemanian Advocate, Vol. 35 #8 1896 The problem of susceptibility to mercury is essentially that doses of mercury harmless to most people produce a dramatic neurological disease in a few. Apparently the few had been healthy before exposure to mercury. Could they be susceptible because they had an otherwise harmless polymorphism which led to excessive mercury being retained, distributed to the brain, or unrestrained from damaging essential neurochemical reactions, or which led to critical reactions being unusually prone to inhibition by mercury? This is the situation in which people would be with the gene defect for Wilson’s disease if they had been raised in an environment entirely free of copper and if they were suddenly moved into ordinary surroundings. Health would quickly change into disease. Vallee’s group raised the possibility that polymorphisms of metallothionein or a related protein could account for the susceptibility, but there was no direct support for this hypothesis. Neal et al. (1941) had pointed out that hatters ill with mercury toxicity often had much lower urinary mercury levels than their healthy workmates. The susceptibility might represent an inability to excrete the metal at an adequate rate. In modern terms, this may be due to a polymorphism.
  43. 43. What brain structures are being poisoned? Alfred Stock’s Theory: the pituitary Eleven autopsies: 6 Hg-free, 5 amalgam bearing. Elevated levels were found in the pituitary. Hg-free: u=78.75 ng/g wet weight, range 40-133 ng/g Hg Amalgam Wearers: u=140, range 40-232 “ The observation that the pituitary gland, which despite its small size, is of such importance for the regulation of the hormonal status, accumulates mercury to levels similar to the kidneys, should be of extreme importance for the mechanism of chronic mercury poisoning. If an above normal Hg-level disturbs the functioning of the pituitary gland as it is known to do with the kidneys (inflammation, anuria, uremia, etc.) then almost all symptoms of the up to now quite mysterious chronic mercury vapor poisoning can be explained. [Understanding the mechanisms at work here] might, in addition to mercury poisoning, be of value also for the treatment of other types of poisoning.” Stock, A, The Mercury Content of the Human Body, Biochemische Zeitschrift 304 1940 73-80
  44. 44. Is there more modern follow-up work? In fact, yes. There are three animal studies now, and three human autopsy studies that are relevant. All of them confirm Stock’s original observation that Hg0 exposure from both fillings and small amounts of Hg0 in the air deposits a relatively high concentration of inorganic mercury into the pituitary. Animal Studies: <ul><li>Maternal-fetal distribution of mercury (203Hg) released from dental amalgam fillings Vimy MJ, Takahashi Y & Lorscheider FL Am J Physiol 258 1990 R939-945
  45. 45. Whole-body imaging of the distribution of mercury released from dental fillings into monkey tissues Hahn LJ, Kloiber R, Leininger RW, Vimy MJ & Lorscheider FL FASEB J 4 1990 3256-60
  46. 46. Dental &quot;silver&quot; tooth fillings: a source of mercury exposure revealed by whole-body image scan and tissue analysis Hahn, LJ, Kloiber R, Vimy MJ, Takahashi Y & Lorscheider FL FASEB J 3 1989 2641-6 </li></ul>Human Studies: <ul><li>Mercury in pituitary glands of dentists Nylander M Lancet feb 22 1986 442
  47. 47. Correlation betwen selenium and mercury in man following exposure to inorganic mercury Kosta I, Byrne AR, Zelenko V Nature 254 1975 238-9
  48. 48. Mercury, selenium, and cadmium in human autopsy samples from Idrija residents and mercury mine workers. Falnoga I; Tusekznidaric M; Horvat M; Stegnar P Environmental Research; 84 (3) p211-218 NOV 2000 </li></ul>
  49. 49. Dental &quot;silver&quot; tooth fillings: a source of mercury exposure revealed by whole-body image scan and tissue analysis Hahn, LJ, Kloiber R, Vimy MJ, Takahashi Y & Lorscheider FL FASEB J 3 1989 2641-6
  50. 50. This unlucky monkey got 16 radio-active mercury fillings placed in his teeth, and was killed on day 28. Whole-body imaging of the distribution of mercury released from dental fillings into monkey tissues Hahn LJ, Kloiber R, Leininger RW, Vimy MJ & Lorscheider FL FASEB J 4 1990 3256-60
  51. 51. Sheep Tissue Accumulation Monkey Tissue Accumulation Notice how, in comparison to all the brain regions tested, the pituitary accumulates several-fold higher amounts of mercury. Interestingly, this disparity is even MORE pronounced in the monkey, an animal that chews less than a sheep.
  52. 52. 3-5 Fetal Lambs exposed in utero after mother’s amalgam placement 5 adult ewes autopsied at different times after amalgam placement Maternal-fetal distribution of mercury (203Hg) released from dental amalgam fillings Vimy MJ, Takahashi Y & Lorscheider FL Am J Physiol 258 1990 R939-945 Mothers Detox Dental Mercury Into their Babies
  53. 53. Mercury in pituitary glands of dentists Nylander M Lancet feb 22 1986 442 Mercury toxicity from industrial exposure II. Battigelli MC J Occup Med 2 1960 394-8 MODERN EVIDENCE: <ul><li>Mercury from dental amalgam accumulates in the human pituitary
  54. 54. Mercury produces pathological changes in the pituitary – It's not an essential trace mineral, and it’s not just harmlessly hanging around playing paddycake. </li></ul>
  55. 55. Different forms of Mercury all have d ifferent tissue distributions and do different nasty things to you. Dental Fillings release a lot of ELEMENTAL MERCURY, also called METALLIC MERCURY or simply MERCURY VAPOR, denoted chemically as: Hg0. Exposure to the vapor results in more than 10x as much Hg accumulating in the brain compared to exposure to equal amounts of injected mercury salts, Hg2+. Once mercury vapor has circulated through your blood stream for a while it is taken up by the red blood cells and the enzyme catalase oxidizes it into one of the two forms of INORGANIC MERCURY, both being Hg2+.
  56. 56. “ In animal experiments, mercury concentrates in the cerebellum, hypothalamus, and areas adjacent to the lateral ventricles and the area postramus.” -- Arena JM, Ed., Poisoning: Toxicology . Symptoms . Treatments, 5 th edition, Thomas Books, 1974 “ Mercury vapor readily crosses cell membranes, including the blood-brain barrier. Autoradiographic studies show that inorganic mercury (Hg2+) does not penetrate the blood-brain barrier but accumulates in areas such as the pituitary gland and area postrema where the anatomical barrier is normally absent.” -- Verity MA and Sarafian TA, Mercury and Mercury Compounds, p. 763, in: Experimental and Clinical Neurotoxicology, 2 nd edition, Spencer & Schaumberg, Eds., Oxford U. Press, 2000 After mercury vapor oxidizes into inorganic mercury it still hits the brain.
  57. 57. Growth Hormone, Arcuate Nucleus & Median Eminence Mercury in the rat hypothalamic arcuate nucleus and median eminence after mercury vapor exposure Ernst, E, Christensen M-E, Hyldgaard Poulsen E Exp Mol Pathol 58 1993 205-14 Mercury was observed in both the arcuate nucleus and median eminence of two groups of rats exposed to Hg0. <ul><li>One group was exposed to 50 ug/M3, 6 hours a day, 5 days a week, for 8 weeks.
  58. 58. Another group was exposed to 400 ug/M3, 6 hours a day, 5 days a week, for 2 weeks only.
  59. 59. The 2 remaining groups of rats didn’t evidence any mercury deposition after exposure to 50 ug/M3 for either 1 week or 4 weeks. </li></ul>This is important because: <ul><li>The Arcuate Nucleus is responsible for growth hormone regulation.
  60. 60. The Median Eminence is a major “switching station” where releasing hormones that are produced in the hypothalamus are transferred to the anterior pituitary where they stimulate the release of adrenal, thyroid and sex hormones, along with prolactin. </li></ul>
  61. 61. Let’s take this apart piece by piece . . . Now that we have tracked the neurotoxin to the pituitary and hypothalamus, let’s see what symptoms of mercury poisoning can be correlated with the known functions of these brain structures. There are two areas to look at: <ul><li>The Posterior Pituitary, Median Eminence and Arcuate Nucleus – the areas most susceptible to Hg2+ because they lack a BBB, and
  62. 62. The Hypothalamus in general. </li></ul>Specifically, we’ll look at: <ul><li>Oxytocin behavioral functions
  63. 63. Vasopressin behavioral functions
  64. 64. Growth hormone behavioral functions
  65. 65. Behavioral effects of disrupting normal functioning in various hypothalamic nuclei </li></ul>
  66. 66. Oxytocin, the “love” and “anti-stress” hormone, isn’t just for milk let-down during nursing . . .
  67. 67. Uvans-Moberg, K; The Oxytocin Factor: Tapping the Hormone of Calm, Love and Healing; Boston: Da Capo Press 2003
  68. 68. Uvans-Moberg, K; The Oxytocin Factor: Tapping the Hormone of Calm, Love and Healing; Boston: Da Capo Press 2003
  69. 69. Uvans-Moberg, K; The Oxytocin Factor: Tapping the Hormone of Calm, Love and Healing; Boston: Da Capo Press 2003
  70. 70. Vasopressin, the “pay attention and remember” hormone, isn’t just for pee-free nights . . .
  71. 71. Harrison's Principles of Internal Medicine 16th Edition © 2005 McGraw-Hill, P.2089 ADULT GH DEFICIENCY (AGHD) This disorder is usually caused by hypothalamic or pituitary somatotrope damage. Acquired pituitary hormone deficiency follows a typical sequential pattern whereby loss of adequate GH reserve foreshadows subsequent hormone deficits. The sequential order of hormone loss is usually GH -> FSH/LH -> TSH -> ACTH. PRESENTATION AND DIAGNOSIS Patients may experience social isolation, depression, and difficulty in maintaining gainful employment. Adult hypopituitarism is associated with a threefold increased cardiovascular mortality rate in comparison to age- and sex-matched controls, and this may be due to GH deficiency. Human Growth Foundation’s Patient Education Manual Growth Hormone isn’t just to make short kids grow taller Clinical Presentation: Impaired quality of life     Decreased energy and drive     Poor concentration     Low self-esteem     Social isolation Body composition changes     Increased body fat mass     Central fat deposition     Increased waist-hip ratio     Decreased lean body mass Reduced exercise capacity Reduced maximum O 2 uptake     Impaired cardiac function     Reduced muscle mass Cardiovascular risk factors     Impaired cardiac structure and function     Abnormal lipid profile     Decreased fibrinolytic activity     Atherosclerosis
  72. 72. Finally, we have reasonable hormonal candidates for explaining the emotional and behavioral changes reported in “erethismus mercurialis” <ul><li>Depression
  73. 73. Memory defect for people
  74. 74. Memory defect for novel information
  75. 75. Feelings of sheer stupidity
  76. 76. Desire to be alone
  77. 77. Fearfulness and Anxiety
  78. 78. Profound fatigue
  79. 79. Manic Depression
  80. 80. Obsessiveness </li></ul><ul><li>Low Oxytocin (OXT), Vasopressin (VP) and Growth Hormone (GH)
  81. 81. Low OXT and VP
  82. 82. Low VP and GH
  83. 83. Low VP and GH
  84. 84. Low OXT and GH
  85. 85. Low OXT and GH
  86. 86. Low Growth Hormone
  87. 87. Alterations in Vasopressin
  88. 88. Low Oxytocin </li></ul>Reported Symptom in Hg Poisoning Hormonal Correlate or Modulator of Symptom
  89. 89. Hypothalamic Structures Hypothalamic Lesions There’s more damage to be done. . . Melmud, Shlomo, The Pituitary, 2 nd Edition, Blackwell Publishing, 2002 Mercury is a glutaminergic excitotoxin, meaning that it can make neurons fire to death by allowing too much glutamate to accumulate.
  90. 90. Hypothalamic Structures Hypothalamic Lesions Melmud, Shlomo, The Pituitary, 2 nd Edition, Blackwell Publishing, 2002
  91. 91. Hypothalamic Structures Hypothalamic Lesions Melmud, Shlomo, The Pituitary, 2 nd Edition, Blackwell Publishing, 2002
  92. 92. Mercury vapor without Booze (above) After inhaling Hg0 for one hour, this mouse was killed an hour later. High concentrations of mercury were encountered in the nasal mucosa, trachea, lung, myocardium, adrenal cortex, kidney, brown fat and especially in the brain . Mercury vapor with Booze (right) This mouse was treated with ethyl-alcohol (2 g/kg body weight, intra-peritoneally injected) 30 minutes before it inhaled mercury vapor for one hour, then was killed an hour later. While the mercury concentration increased in the liver as compared to the “dry” mouse, mercury decreased in the lung, myocardium, brown fat , and very conspicuously in the brain . Experimental evidence to support the therapeutic, neuroprotective, benefits of alcoholism . . . Khayat A, Dencker L, Whole Body and Liver Distribution of Inhaled Mercury Vapor in the Mouse: Influence of Ethanol and Aminotriazole Pretreatment. J Applied Toxicology 3 1983 66-74 “ A 44 year old dentist presented with marked finger tremor, visual deterioration, poor memory for recent events and a tendency to be irritable and argumentative. In the previous year he had felt vaguely unwell with headaches, muscle pains, 14 kg weight loss and a disturbed sleep pattern. Alcohol improved the symptoms leading to unfounded suspicions that alcoholism was the underlying problem.” Symington IS, Cross DC, Dale IM, Lenihan JMA, “Mercury Poisoning in Dentists” J. Soc. Occup. Med. (1980) 30, 37-39
  93. 93. The Joys of Working in a Dental Office Uzzell BP & Oler J, Chronic low-level mercury exposure and neuropsychological functioning J Clin Exp Neuropsychology 8 1986 581-93
  94. 94. The Great Tennessee Mercury Vapor Accident (how to give your patients inadequate care and still get published) Elemental Mercury Vapour Toxicity, Treatment, and Prognosis After Acute, Intensive Exposure in Chloralkali Plant Workers. Part I: History, Neuropsychological Findings and Chelator Effects. Bluhm RE, Bobbit RG, Welch LW, Wood AJJ, Bonfiglio JF, Sarzen C, Heath AJ, Branch RA Human & Experimental Toxicology 11 (3) p201-210 MAY 1992 After an acute exposure, these guys were treated for a total of less than 3 weeks with DMSA, a chelater that doesn’t cross the blood-brain-barrier to remove metals from the CNS
  95. 95. Erethism Cured with Aggressive Chelation Therapy Chronic elemental mercury intoxication: neuropsychological follow-up case study. Hua MS, Huang CC, Yang YJ, Brain Inj 1996 May 10(5):377-84 A few years later, in Taiwan, a more severely poisoned lampsocket worker was treated for 2 months with NAP, a chelator that crosses the blood-brain-barrier. Unlike the workers studied by the doctors in America, this man got better.
  96. 96. “ There is a principle which is a bar against all information, which is proof against all argument, and which cannot fail to keep man in everlasting ignorance. “ That principle is condemnation without investigation.” Herbert Spencer “ Don’t worry about what the world wants from you, worry about what makes you come more alive. Because what the world really needs are people who are more alive.” Lawrence Le Shan “ One must have teeth. Then love’s like biting into an orange when the juice squirts in your teeth.” Bertolt Brecht “ A test of what is real is that it is hard and rough. Joys are found in it, not pleasure. What is pleasant belongs to dreams.” Simone Weil