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The following selection of abstracts form part of ASOMAT's submission to NHMRC in June 1998

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Index of Abstracts

Assessment of mercury in mouth air (12)

Biomonitoring for the evaluation of Hg from amalgam fillings. Mercury determination in urine before and after oral doses of 2,3-dimercapto-1-propanesulfonic acid (DMPS) and in hair (15)

Calcium-Selenium Mercury Connection in Cancer and Heart Disease (13)

Cardiac and Aortic Lesions in Chronic Experimental Poisoning With Mercury Vapors (45)

Chronic inhalation of low-level Hgo can inhibit polymerization of tubulin (20)

Comparative Epidemiology of Multiple Sclerosis and Dental Caries (7)

Contact allergy to mercury is suggested as a possible etiologic factor of mucosal changes (27)

Daily Dose Calculations from Measurements of Intra-oral Mercury Vapor (26)

Deleterious Effects of Low Micromolar Mercury on Important Brain and Cerebrospinal Fluid Proteins (30)

Dental amalgam mercury controversy-Inorganic mercury and the CNS; genetic linkage of mercury and antibiotic resistances in intestinal bacteria (19)

Dental amalgam mercury daily dose estimated from intra-oral vapor measurements: A predictor of mercury accumulation in human tissues (41)

Dental care using silver amalgam (39)

Determination and metabolism of dithiol chelating agents. XII. Metabolism and pharmacokinetics of sodium 2,3-dimercaptopropane-1- sulfonate in humans (23)

Diagnosis of Heavy Metal Loading by the Oral DMPS and chewing gum tests. (14)

Does mercury from amalgam restorations constitute a health hazard? (42)

Effect of Subchronic Mercury Exposure on lectrocorticogram of Rats (9)

Effects of dose of elemental mercury and first-pass circulation time on exhalation and organ distribution of inorganic mercury in rats (22)

Effects of exercise training on the distribution of metallic mercury in mice (34)

Effects of metal cations on pituitary hormone secretion in vitro (6)

Effects of Inorganic Mercury and Methylmercury on the Ionic Currents of Cultured Rat Hippocampal Neurons (38)

Epidemiological Study of Mercury Sensitization (33)

Factors influencing mercury evaporation rate from dental amalgam fillings. (3)

Increased Adhesion and Activation of Polymorphonuclear Neutrophil Granulocytes to Endothelial Cells under Heavy Metal Exposure (17)

Inorganic mercury is transported from muscular nerve terminals to spinal and brainstem motoneurons.(2)

Mercury released from dental "silver" fillings provokes an increase in mercury- and antibiotic-resistant bacteria in oral and intestinal floras of primates (37)

Mercury concentrations in the human brain and kidneys in relation to exposure from dental amalgam fillings (25)

Mercury Vapour Inhalation Inhibits Binding of GTP to Tubulin in Rat Brain: Similarity to a Molecular Lesion in Alzheimer Diseased Brain. (29)

Mercury Release From Amalgam Into Saliva: (21)

Mercury from silver dental fillings (amalgam) may be related to multiple sclerosis (36)

Mercury in cerebrospinal fluid in multiple sclerosis (5)

Mobilized mercury in subjects with varying exposure to elemental mercury vapour (24)

New Aspects of Murine Coxsackie B3 Myocarditis--Focus on Heavy Metals. (16)

Oral mucosal lesions related to silver amalgam restorations. (4)

Relationship between mercury from dental amalgam and the cardiovascular system (35)

Relationship between mercury concentration in human organs and different predictor variables (43)

Resistance of the Normal Human Microflora to Mercury and Antimicrobials After Exposure to Mercury From Dental Amalgam Fillings (11)

Retrograde Axonal Transport of Mercury in Primary Sensory Neurons Innervating the Tooth Pulp in the Rat (32)

Serial measurements of intra-oral air mercury: estimation of daily dose from dental amalgam (40)

Side-effects: mercury contribution to body burden from dental amalgam (31)

Silver Concentrations in Human Tissues, Their Dependence on Dental Amalgam and Other Factors (10)

Total and Inorganic Mercury in Breast Milk in Relation to Fish Consumption and Amalgam in Lactating Women. (28)

Toxicity of Ionic Mercury and Elemental Mercury Vapour on Brain Neuronal Protein (18)

Trace element imbalances in isolated subcellular fractions of Alzheimer's disease brains. (44)

Traces of mercury in organs from primates with amalgam fillings. (8)

Urinary mercury after administration of 2,3-dimercaptopropane-1- sulfonic acid: correlation with dental amalgam score (1)

 

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Abstracts

1. Aposhian HV Bruce DC Alter W Dart RC Hurlbut KM Aposhian MM Urinary mercury after administration of 2,3-dimercaptopropane-1- sulfonic acid: correlation with dental amalgam score. FASEB J (1992 Apr) 6(7):2472-6

ABSTRACT: The April 1992 issue of FASEB includes a study done at the University of Arizona by Professor H. Vasken Aposhian and his colleagues demonstrating that two-thirds of the mercury excreted in the urine of those with dental amalgams appears to be derived originally from the mercury vapor released from their amalgams.5 A unique feature of this study was the development of an "amalgam score." The amalgam score was calculated on the basis that a tooth has five visible sides. If an amalgam surface was 1 mm or less it was given a score of 1; a diameter above 1 and less than 2 mm received a score of 2; and a diameter of 3 mm or more a score of 3. The amalgam score is the sum of the score of all amalgam surfaces on all teeth in the subjects mouth. The administration of 300 mg of DMPS by mouth increased the mean urinary mercury excretion of the amalgam group from 0.70 to 17.2 ug and that of the nonamalgam group from 0.27 to 5.1 ug over a nine hour period. There was a highly significant positive correlation between the mercury excreted in the urine two hours after DMPS administration and the dental amalgam scores. "The results of the present experiments show that there is a pool of inorganic mercury in the human body that can be mobilized by administering the chelating agent DMPS and that more mercury is excreted by individuals with amalgams than those without."

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2. Arvidson B. Inorganic mercury is transported from muscular nerve terminals to spinal and brainstem motoneurons. Muscle Nerve. 15(10):1089-1094, Oct 1992.

ABSTRACT: The distribution of mercury within the brainstem and spinal cord of mice was investigated with the autometallographic technique after intramuscular administration of a single dose of mercuric mercury (HgCl2). Deposits of mercury were localized to motor neurons of the spinal cord and to brainstem motor nuclei; i.e., neurons with their peripheral projections outside the blood-brain barrier. Unilateral ligation of the hypoglossal nerve prior to the injection of HgCl2 prevented the accumulation of mercury deposits in the ipsilateral hypoglossal nucleus. The selective accumulation of mercury in spinal and brainstem motoneurons is most probably due to a leakage of metal-protein complexes from capillaries in muscle into myoneural junctions, followed by uptake into nerve terminals and retrograde axonal transport. The possible link between this process and the development of motor neuron degeneration in ALS is discussed.

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3. Bjorkman L; Lind B Factors influencing mercury evaporation rate from dental amalgam fillings. Address: Department of Environmental Hygiene, Karolinska Institutet, Stockholm, Sweden Scand J Dent Res, 100: 6, 1992 Dec, 354-60

ABSTRACT: Factors influencing mercury evaporation from dental amalgam fillings were studied in 11 volunteers. Air was drawn from the oral cavity for 1 min and continuously analyzed with a mercury detector. In six volunteers the median unstimulated evaporation rate was 0.1 ng Hg/s, range 0.09-1.3 ng Hg/s. After chewing gum for 5 min the highest evaporation rate was 2.7 ng Hg/s. Chewing paraffin wax gave only a small increase in evaporation rate. Changes in airflow rates between 1.5 and 2.5 1/min during the 1 min sampling did not change the amount of mercury drawn from the oral cavity. Sampling with different mouthpieces and closed mouth was compared to open mouth sampling with a thin plastic tube. It was found that the latter method could result in lower values for some volunteers due to simultaneous mouth breathing. After placing individual plastic teeth covers in the mouth, the intraoral evaporation of mercury decreased immediately by 89- 100% of previous levels. This technique could be used to detect mercury evaporation from separate amalgam fillings or to reduce the intraoral mercury vapor concentration. Rinsing the mouth with heated water for 1 min increased the mean evaporation rate by a factor of 1.7 when the water temperature increased from 35 degrees C to 45 degrees C.

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4. Bolewska-J; Hansen-HJ; Holmstrup-P; Pindborg-JJ; Stangerup-M Oral mucosal lesions related to silver amalgam restorations. Department of Oral Medicine and Oral Surgery, University Hospital, Copenhagen, Denmark. Oral-Surg-Oral-Med-Oral-Pathol. 1990 Jul; 70(1): 55-8

ABSTRACT: : A total of 49 consecutive patients with lesions of the oral mucosa that were in contact with corroding dental amalgam restorations were subdivided into two groups. In group 1 the lesions were restricted to the contact area opposing the dental restoration, whereas the extent of the lesions in group 2 exceeded that of the contact area. Epicutaneous test for mercury allergy showed that a significantly greater proportion of the patients in group 1 had positive reactions to mercury than in group 2 (p = 0.019). The amalgam restorations were replaced by composite resin or porcelain fused to gold crowns, or contact between amalgam fillings and oral mucosa was prevented by an acrylic splint. After this treatment regression of lesions was far more pronounced in group 1 than in group 2 ( p less than 0.001). On the basis of these findings, contact allergy to mercury is suggested as a possible etiologic factor of the mucosal changes in group 1, and the designation contact lesion is proposed for such lesions. The lesions of patients in group 2 seem unrelated to a contact allergy to mercury, and other causes such as lichen planus should be considered.

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5. Britt Ahlrot-Westerlund. Mercury in cerebrospinal fluid in multiple sclerosis. Swed J. Biol Med 1 :6, Mar 1989.

ABSTRACT: Average mercury concentration in cerebrospinal fluid in healthy controls was 0.4 ug/l (range 0.1-1.2) and in multiple sclerosis cases it was 3.0 (1. 5-5.4). In some cases treatment with antioxidation therapy (selenium, vitamins) and/or removal of amalgam cured/improved patients with MS. It is thus possible that mercury poisoning may constitute part of the etiology.

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6. Cooper RL, Goldman JM, Rehnberg GL, McElroy WK, Hein JF. Effects of metal cations on pituitary hormone secretion in vitro. J Biochem Toxicol. 2:241-9. Fall-Winter 1987.

ABSTRACT: Increased body burdens of metal cations are known to affect adversely reproductive function in several species. The effects of these metals on gonadal function are well documented. In contrast, little is known about their possible direct effects on pituitary hormone release. The purpose of this study was to determine, in vitro, the effects of nickel, cadmium, and zinc (50 microM) on both baseline and potassium chloride (KCl)-stimulated pituitary luteinizing hormone (LH), prolactin (PrL), and thyroid- stimulating hormone (TSH) release. Anterior pituitary fragments from adult male Long-Evans rats were evaluated using a continuous-flow perfusion system. Baseline and stimulated LH releases were unaffected by nickel and zinc; however, cadmium caused an increase in baseline LH secretion. Baseline PrL release was decreased by zinc, while cadmium resulted in increased release of this hormone. Stimulated PrL release was lower during exposure to zinc but unaltered by nickel and cadmium. Following exposure to zinc, a rebound in stimulated release was noted for all three hormones measured. These results showed that the metal cations tested did have a direct effect on pituitary hormone release at a dose lower than those reported to alter testicular function in vitro. Furthermore, the changes in pituitary hormone secretion varied depending upon the metal and hormone being evaluated.

ASOMAT COMMENT: Dr. Magnus Nylander, at the Karolinska Institute in Sweden, has conducted autopsy studies demonstrating that dental personnel have severely elevated levels of mercury in the pituitary gland. He has also found that the levels of mercury in the pituitary gland correlate to the number of dental amalgam fillings present in subjects. It has also been scientifically proven that mercury is more toxic and active chemically than nickel, cadmium or zinc. This study demonstrates the potential of mercury to dramatically alter hormones produced by the pituitary, the master gland of the body. It must also be remembered that nickel alloys are used in most dental crowns (caps) and that research has proven patient exposure to nickel from these crowns.

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7. Craelius W Comparative Epidemiology of Multiple Sclerosis and Dental Caries. published J. Epidemiology and Community Health 1978, 32, 155- 165

ABSTRACT: Causal comparison of the WHO map of dental caries incidences throughout the world reveals a striking parallel in general trend. Comparison of decayed, missing and filled teeth with the MS death rates results in a correlation coefficient of 0.97, and the probability of a chance occurrence is less than 0.002. This represents a nearly perfect linear relationship between dental disease rates and MS death rates.

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8. Danscher-G; Horsted-Bindslev-P; Rungby-J Traces of mercury in organs from primates with amalgam fillings. Department of Neurobiology, University of Aarhus, Denmark. Exp-Mol-Pathol. 1990 Jun; 52(3): 291-9

ABSTRACT: In order to trace possible accumulations of mercury, three vervet monkeys received occlusal amalgam fillings, three others maxillary bone implants of amalgam, and three untreated monkeys served as controls. One year later all animals were sacrificed by transcardial perfusion with glutaraldehyde. Tissue sections from different organs were subjected to silver amplification by autometallography and analyzed at light and electron microscopical levels. It was found that amalgam fillings (total, 0.7-1.2 g) caused deposition of mercury in the following tissues: spinal ganglia, anterior pituitary, adrenal, medulla, liver, kidneys, lungs, and intestinal lymph glands. In monkeys with maxillary silver amalgam implants ( total, 0.1-0.3 g), mercury was found in the same organs except for liver, lungs, and intestinal lymph glands. Organs from the three control animals were devoid of precipitate. To evaluate whether silver released from the corroding amalgam fillings added to the staining pattern, tissue sections were exposed to potassium cyanide prior to being autometallographically developed. This treatment removes all traces of silver, leaving mercury sulfide accumulation untouched. By comparing sections that had been exposed to cyanide with untreated parallels no difference was seen in the pattern confirming that mercury was the only catalyst present in the tissue. These results strongly support what has been suggested previously that dental fillings in primates cause absorption of mercury released from amalgam fillings through lungs and intestinal tract, and that depending on exposure mercury is distributed to most organs and will eventually be found in the central nervous system.

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9. Desi, I; Nagymadtenyi, L; Schulz, H. Effect of Subchronic Mercury Exposure on lectrocorticogram of Rats. Neurotoxicology, 17(3-4):719,23, 1996.

ABSTRACT: Mercury is a neurotoxic compound causing irreversible disorders of the central and peripheral nervous system. In some of the previous human and experimental studies mercury also affected some functional neurological parameters such as EEG, and cortical evoked potentials. In the present study, the effect of subchronic (4, 8, and 12 weeks) relatively low level (0.4, 0.8, and 1.6 mg/kg mercury in form of HgC12, per os Savage) treatment on the basic cortical activity was investigated. Certain parameters of electrocorticogram (EcoG) recorded simultaneously from the primary somatosensory, visual and auditory centers were analyzed. The results showed that mercury had a dose- and time-dependent effect on the examined EcoG parameters, and the changes became significant by the end of the experiment of week 12.

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10. Drasch, G; Gath, HJ; Heissler, E; Schupp, I; Roider, G. Silver Concentrations in Human Tissues, Their Dependence on Dental Amalgam and Other Factors. J Trace Elements in Medicine and Biology; 9(2):82-7, 1995.

ABSTRACT: Human tissue samples (Liver, Kidney cor tex, five brain regions: grey matter of cerebrum, white matter of cerebrum, nucleus lentiformis, cerebellum, brain stem) from 173 deceased persons were analyzed for silver (Ag) by GF-AAS (Graphite Furnace Atomic Absorption Spectrome try) and the results compared with the number of teeth with amalgam fillings and the concentration of inorganic mercury (Hg), which had been determined in the same tissue samples in a previous study. It was found that the mean Ag concentrations in liver and brain of adult females are approximately twice that of males. Moreover, the Ag concentrations, especially in the brain, depend possibly on age. To exclude these confounding factors as far as possible, the influence of dental amalgam and the correlation of Ag and Hg were evaluated only in a sub-group of 93 males, aged 11-50 years. In this sub-group statistically significant correlations were found between the number of teeth with dental amalgam and the Ag concentrations in the cerebral cortex and the liver. No such correlation was found for the kidney. Ag and inorganic Hg correlate well in this sub-group in the liver, but not in the cerebral cortex or the kidney. concentrations (mcg/kg in tissue wet weight, geometric mean) of 1.59 and 5.41 in the grey matter of cerebrum,1.42 and 4.25 in the white matter of cerebrum, 1.53 and 4.89 in the nucleus lentiformis, 1.95 and 5.02 in the cerebellum,1.05 and 3.27 in the brain stem 3.40 and 8.15 in the liver and 0.42 and 0.44 the kidney cortex In contrast comparing all individuals under investigation with only 0-2 teeth with amalgam no correlation between Ag and inorganic Hg could be found in liver, kidney cortex or cerebral cortex. These results show that amalgam fillings release Ag as well. Considering the different toxicokinetics of Ag and Hg it can be concluded that Ag is a reliable marker for the fact that the elevated concentrations of inorganic Hg found in tissues of individuals with amalgam fillings derive mainly from these fillings and not from other theoretically possible sources.

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11. Edlund, C; Bjorkman, L; Ekstrand, J; Sandborgh-Englund, G; Nord, CE. Resistance of the Normal Human Microflora to Mercury and Antimicrobials After Exposure to Mercury From Dental Amalgam Fillings. Clin Infect Dis., 22(6):944-950, June 1996.

ABSTRACT: The concentrations of mercury in saliva and feces and the resistance pattern of the gastrointestinal microflora were investigated for 20 subjects. Ten patients, with a mean number of 19 amalgam moved during one dental session. Ten subjects without amalgam fillings served as a control group. Saliva and fecal samples were collected before amalgam removal and 2, 7, 14, and 60 days afterward. Mercury levels in saliva and feces correlated significantly with the number of amalgam surfaces. No differences in the resistance pattern of the oral microflora were detected between the two groups. In the amalgam group there was an increase in the relative number of intestinal microorganisms resistant to mercury, ampicillin, cefoxitin, erythromycin, and clindamycin on days 7-14. This was not statistically significant in light of the normal variations of the control group. A significant correlation between the prevalence of mercury resistance and multiple antimicrobial resistance in intestinal bacterial strains was observed

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12. Emler , Cardone, "An assessment of mercury in mouth air", Oral Roberts University, March 1985

ABSTRACT: In 1985, a study at Oral Roberts University involved pediatric dental patients between the ages of five and twelve. The object of the study was to measure levels of mercury vapor in the mouth before and after installation of amalgam fillings. The study concluded that "dental amalgam restorations and mercury vapor exposure were shown to be related" and "chewing increases the evaporation of mercury from dental amalgams that are only 1week old."

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13. Foster, HD. Landscapes of Longevity: The Calcium-Selenium Mercury Connection in Cancer and Heart Disease. Med Hypotheses, 48(4):355-60, 1997.

ABSTRACT: Cancer and heart disease display spatial patterns that suggest the possible involvement of calcium and selenium deficiencies and mercury excess in their aetiologies. As a consequence, longevity tends to be most common in regions where the environment is calcium and selenium enriched but contains only low levels of mercury. Examples are cited from West Africa, China, England and the USA

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14. Gerhard I: Waldbrenner P; Thuro H; Runnebaum B. Diagnosis of Heavy Metal Loading by the Oral DMPS and chewing gum tests. Clinical Lab. 38: 404-11

ABSTRACT: A study of 490 women in the hormone and sterility lecture course, besides the usual endocrinologic diagnostic workup, the heavy metal flushing test was performed with DMPS. Urine concentrations of Mercury, lead, Arsenic, Cadmium, Copper, were determined by Atomic Absorption Spectroscopy (ASS) and corrected for creatinine clearance. zinc and Selenium concentrations were also measured in base line urine samples. Saliva Mercury levels were also determined after a 10 minute chewing session. Over 90% of all baseline mercury concentrations lay under 5 mcg/g creatinine. After DMPS challenge over 25% of the women excreted over 100mcg/g creatinine. In women who had over 500 mcg/g creatinine there were no cases of spontaneous pregnancy. Underweight and Hperandrogenous women in particular had significantly elevated mercury levels.Salivary mercury levels wee in a direct proportion to the number of amalgams in the mouth, both before and after chewing.." Women with higher mercury excretion in the urine showed almost 5 times higher mercury values in the saliva after gum chewing. CONCLUSION: Heavy metal exposures were present in about half of the patients with infertility and hormonal disorders.

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15. Herrmann-M; Schweinsberg-F Abteilung Allgemeine Hygiene und Umwelthygiene, Universitat Tubingen.Zentralbl-Hyg-Umweltmed. Biomonitoring for the evaluation of Hg from amalgam fillings. Mercury determination in urine before and after oral doses of 2,3-dimercapto-1-propanesulfonic acid (DMPS) and in hair 1993 May; 194(3): 271-91

ABSTRACT: The statistically significant correlation between mercury urine concentrations of 67 male volunteers aged 16 to 72 years (mean: 1.20 micrograms/l, range 0.1-5.0; 1.57 micrograms/24 h, range 0.1-7.8) and their amalgam filling index (r = 0.653; p < or = 0.0001) indicates that amalgam fillings burden the organism with mercury.

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16. Ilback, NG; Lindh, U; Fohlman, J; Friman, G. New Aspects of Murine Coxsackie B3 Myocarditis--Focus on Heavy Metals. Eur Heart J, 16(Suppl 0):20-4, 1995.

ABSTRACT: The magnitude of inflammatory lesions in the hearts of coxsackie B3 (CB3)-virus infected mice can be affected by the potentially toxic heavy metals cadmium (Cd), nickel (Ni) and methyl mercury (MeHg). The infection is associated with a changed distribution, such as Cd accumulation in the spleen and kidneys. New target organs for Ni during the infection were the heart, pancreas and lungs in which inflammatory lesions were present. This increased uptake was correlated with the disturbed function of immune cells and an increased inflammatory reaction.

Ni and MeHg appeared to have a direct effect on immune cells that resulted in changed natural killer cell activity and decreased mobilization of macrophages, CD4+ and CD8+ cells into the inflammatory lesions.

Although MeHg increased spleen T cell activity and gamma-interferon (IFN- gamma) levels, the inflammatory lesions in the heart increased. Another detrimental effect of MeHg treatment was evident by an increased calcium and decreased zinc content in the inflamed heart, which may partly explain the more severe inflammatory lesion. The host's response, CB3 infection, changed the distribution of each metal in a specific way, a fact which may subsequently result in altered target organ toxicity and resistance to the infection

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17. Klein, CL; Kohler, H; Kirkpatrick, CJ. Increased Adhesion and Activation of Polymorphonuclear Neutrophil Granulocytes to Endothelial Cells under Heavy Metal Exposure in Vitro. Pathobiology. 62(2):90-98,1994.

ABSTRACT: Heavy metals have been implicated in the mechanisms of endothelial damage. Influences of heavy metal ions on diverse cell types have been studied using a variety of in vitro and in vivo methods. Polymorphonuclear neutrophil granulocytes (PMNs) have physiological and pathological functions, including the modulation of adhesion to and destruction of endothelial cells (Ecs).PMNs were studied during interaction with human umbilical vein Ecs under exposure to zinc, nickel and cobalt using an in vitro model. We studied adhesion processes with the help of a computer-controlled image-analyzing system and examined the activation of PMNs by quantification of leukotriene B4 ( LTB4) release. The biphasic effects of the valuated heavy metals on PMN-EC adhesion, with stimulation at very high and very low molar concentrations, were observed. The release of LTB4 by PMNs increased during exposure to very low metal concentrations. The initiation of these important pathogenetic mechanisms of inflammation at very low metal ion concentrations, which give no morphologic changes, must be regarded as potentially significant with respect to the toxic effects of heavy metals.

ASOMAT COMMENT: Damage to the endothelium is widely regarded as the initial step in the process that leads to cardiovascular disease. Although mercury was not included in this study, it is a heavy metal that has previously been shown to cause endothelial damage. The three metals examined in this study (nickel, cobalt and zinc) are all used in dental materials. Research, has demonstrated the release and bioavailability of nickel (and mercury). Cardiovascular disease has become widespread only since the 1920's, about the time of increased use of heavy metals in dental therapy and long after humans consumed eggs, meat, milk, butter and cheese.

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18. Lorscheider, FL; Vimy, MJ; Pendergrass, JC; Haley, BE. Toxicity of Ionic Mercury and Elemental Mercury Vapour on Brain Neuronal Protein Metabolism. 1994

ABSTRACT: Recent studies have demonstrated that Hg is selectively concentrated in human brain regions involved with memory function, and may be implicated in the aetiology of Alzheimer's Disease (AD). Abnormal microtubule formation in AD brains has been associated with a defect in the tubulin polymerization cycle (Khatoon et al. Ann Neurol., 26:210-215, 1989) which may increase the density of neurofibrillary tangles. A similar tubulin defect can be induced in the brain of HgCI2-treated rats, suggesting a connection between exposure to inorganic Hg and AD (literature reviewed in Goering et a]., ibid). We have also demonstrated that HgCl2 markedly inhibits in vivo ADP-ribosylation of rat tubulin and therefore alters a specific neurochemical reaction involved in maintain-ing brain neuron structure (Palkiewicz et al. Neurochem., 62:049-2052: 1994). In our present investigations 3 groups of rats were exposed to Hg vapour 4 h/day for 0, 2 or 14 consecutive days. Vapour concentration during exposure periods was maintained at 300 mcg Hg/m air, a level detectable in mouths of some human subjects with large numbers of amalgam fillings. Cold vapour atomic fluorescence spectrometry (Winfield et al.. Clin Chem., 40:206-210, 1994) revealed average brain Hg concentrations after 0, 2 and 14 days exposure to be 10, 108 and 396 ng/g tissue (wet wt.) respectively. Photoaffinity labe]ling of the beta-subunit of the tubulin dimer with [ a32P@8N3GTP in brain homogenates was partially diminished after 2 days, and very markedly diminished after 14 days of Hg vapour exposure. Since the rate of tubulin polymeriza-tion is dependent upon binding of tubulin dimers to GTP, we conclude that low-level Hg vapour exposure inhibits the polymerisation of tubulin essential for formation of microtubules.

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19. Lorscheider FL; Vimy MJ; Summers AO; Zwiers H. The dental amalgam mercury controversy-Inorganic mercury and the CNS; genetic linkage of mercury and antibiotic resistances in intestinal bacteria. Toxicology 97(1-3):19-22, Mar 31,1995.

ABSTRACT: Mercury (Hg) vapor exposure from dental amalgam has been demonstrated to exceed the sum of all other exposure sources. Therefore the effects of inorganic Hg exposure upon cell function in the brain and in the intestinal bacteria have recently been examined. In rats we demonstrate that ADP-ribosylation of tubulin and actin brain proteins is markedly inhibited, and that ionic Hg can thus alter a neurochemical reaction involved with maintaining neuron membrane structure. In monkeys we show that Hg, specifically from amalgam, will enrich the intestinal flora with Hg-resistant bacterial species which in turn also become resistant to antibiotics.

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20. Lorscheider, FL; Vimy, MJ; Pendergrass, JC; Haley, B FASEB J. 9(4): A-3845. FASEB Annual Meeting, Atlanta, Georgia, 10th March 1995.

ABSTRACT: Methyl mercury will interact with tubulin causing disassembly of microtubules that function to maintain neurite structure. Numerous reports also establish that mercury vapor (Hgo) is continuously released from "silver" amalgam tooth fillings into mouth air. In the present study rats were exposed to Hgo 4 h/day for 0, 2, 7, 14 and 28 days at 250 mcg Hg/m 3 air, a concentration present in mouth air of some humans with large numbers of amalgam fillings. Average rat brain Hg concentrations increased significantly (40-100 fold) with duration of Hgo exposure. By day 14 of Hgo exposure, photoaffinity labelling of the b-subunit of the tubulin dimer with [a32 P]8N3GTP in brain homogenates was decreased 75%, as seen on analysis of SDS-PAGE autoradiograms. The identical neurochemical lesion of similar magnitude is evident in Alzheimer brain homogenates when compared to human age-matched controls. Since the rate of tubulin polymerization is dependent upon binding of tubulin dimers to GTP, we conclude that chronic inhalation of low-level Hgo can inhibit polymerization of tubulin essential for formation of microtubules.

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21. Lussi, A Mercury Release From Amalgam Into Saliva: An In-Vitro Study.. Schweiz Monatsschr Zahnmed, 103(6):722-6, 1993.

ABSTRACT: The aim of the study was to investigate mercury release into salivary fluid and to test whether this release is associated with flow rate, buffer capacity or pH of salivary fluid. Salivary fluid was collected from 18 persons (11 with amalgam fillings, 7 without) and the surface area of the fillings was assessed. Mercury loss in unstimulated saliva was 11.6 ng/min for persons with amalgam and 2.1 ng/min for those without. Multiple regression analysis revealed no association between flow rate, buffer capacity or pH of unstimulated salivary fluid and mercury release.

COMMENT: The finding of mercury release of 11.6 ng/min in unstimulated saliva translates to a daily exposure of 16.7 micrograms of mercury [11.6 x 60 x 24/1000]. This level is considerably higher than the daily exposure estimates of amalgam mercury provided by dental authorities ( i.e., 1-3 micrograms/day), and much higher than the USPHS Minimal Risk Level (MRL) for mercury exposure for the general population (0.28 micrograms/day). Moreover, the findings of this study, dealing with dissolved mercury, must be added to exposures calculated from mercury vapor measurements, which is directly inhaled mercury, in addition to the consideration of increased mercury release from multiple daily stimulations of amalgams.

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22. Magos L, Clarkson TW, & Hudson AR. The effects of dose of elemental mercury and first-pass circulation time on exhalation and organ distribution of inorganic mercury in rats. Biochem Biophys Acta. 25;991(1):85-9. April 1989.

ABSTRACT: The oxidation of mercury vapor to ionic mercuric mercury is important in limiting the availability of mercury vapor to certain tissues. Thus, after a short residence time in blood (6 seconds after jugular vein injection), 12.9- 17% is exhaled in the first pass of blood as compared to 10.4- 12.2% exhaled with a longer residence time in blood (1.8 seconds after tail vein injection). Furthermore, there was a general tendency, even at 60 seconds after dosing, for certain tissues - lung, brain, and heart - to have higher values after dosing from the jugular vein. The results confirm previous observations that the form of inorganic mercury greatly influences the short-term deposition of mercury in certain tissues. Thus, as compared to ionic mercury, administration of mercury vapor increases lung levels 5-10 fold; brain levels 4-fold; and heart 3-fold. Blood levels are lower after mercury vapor exposure, particularly after higher doses. These findings are consistent with a model wherein mercury vapor is in part oxidized by red blood cells, with the remainder rapidly diffusing in tissue where it is also oxidized to ionic mercury.

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23. Maiorino RM Dart RC Carter DE Aposhian HV Determination and metabolism of dithiol chelating agents. XII. Metabolism and pharmacokinetics of sodium 2,3-dimercaptopropane-1- sulfonate in humans. J Pharmacol Exp Ther (1991 Nov) 259(2):808-14

ABSTRACT: The sodium salt of 2,3-dimercaptopropane-1-sulfonic acid (DMPS) is used p. o. for the treatment of chronic lead and Hg intoxication in humans. The metabolism and pharmacokinetics of DMPS were determined after p.o. administration of 300 mg of DMPS to each of 10 normal young men. The absorbed DMPS was metabolized rapidly and extensively to a disulfide form( s). By 24 hr after DMPS administration, the area under the blood concentration-time curve of unaltered DMPS was 3.9 compared to 143 for altered DMPS. Altered DMPS is the difference between total DMPS and unaltered DMPS. Unaltered DMPS is the unbound, parent compound;, total DMPS consists of unaltered DMPS plus oxidized [disulfide] DMPS which is determined after reduction with dithiothreitol. In blood the altered form was confined to plasma. By 15 hr, only 3.7% of the administered DMPS was excreted in the urine as unaltered DMPS and 38.7% as altered DMPS. The unaltered and altered DMPS represented 9 and 91%, respectively, of the total amount of DMPS in the urine. Altered DMPS was converted to unaltered DMPS by treatment with dithiothreitol, which indicates that the altered DMPS is a disulfide(s). There was a high correlation between the urinary excretion of Hg and the urinary excretion of unaltered DMPS (r = 0.920 +/- 0.022 S.E.).

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24. Molin M; Schutz-A; Skerfving-S; Sallsten-G Mobilized mercury in subjects with varying exposure to elemental mercury vapour. Int-Arch-Occup-Environ-Health. 1991; 63(3): 187-92

ABSTRACT: In a mercury mobilization test, 0.3 g of the complexing agent sodium 2, 3-dimercaptopropane-1-sulfonate (DMPS) was given orally to 10 workers with moderate occupational exposure to elemental mercury vapour, to 8 dentists with slight exposure, to 18 matched controls, and to 5 referents without amalgam fillings. In the workers, DMPS caused an increase in 24-h urinary mercury excretion by a factor of 10; in the dentists, 5.9; in the controls, 5.3; and in the amalgam-free referents, 3.8. Of the mercury excreted during 24 h, 59% appeared during the first 6 h. Close, albeit non-linear, associations were found between mobilized mercury and the premobilization mercury levels in plasma and urine, but not with the duration of occupational exposure or the rough estimate of the integrated function of blood levels vs time. The present data indicate that mercury mobilized after a single DMPS dose in close connection with exposure is mainly an index of recent exposure and is not significantly affected by slow body pools or long-term exposure.

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25. Nylander M Friberg L Lind B Mercury concentrations in the human brain and kidneys in relation to exposure from dental amalgam fillings. Swed Dent J (1987) 11(5):179-87

ABSTRACT: Samples from the central nervous system (occipital lobe cortex, cerebellar cortex and ganglia semilunare) and kidney cortex were collected from autopsies and analysed for total mercury content using neutron activation analyses. Results from 34 individuals showed a statistically significant regression between the number of tooth surfaces containing amalgam and concentration of mercury in the occipital lobe cortex (mean 10.9, range 2. 4-28.7 ng Hg/g wet weight). The regression equation y = 7.2 + 0.24x has a 95% confidence interval for the regression coefficient of 0.11-0.37. In 9 cases with suspected alcohol abuse mercury levels in the occipital lobe were, in most cases, somewhat lower than expected based on the regression line. The observations may be explained by an inhibition of oxidation of mercury vapour. The regression between amalgams and mercury levels remained after exclusion of these cases. The kidney cortex from 7 amalgam carriers (mean 433, range 48-810 ng Hg/g wet weight) showed on average a significantly higher mercury level than those of 5 amalgam-free individuals (mean 49, range 21-105 ng Hg/g wet weight). In 6 cases analysis of both inorganic and total mercury was carried out. A high proportion (mean 77% SD 17%) of inorganic mercury was found. It is concluded that the cause of the association between amalgam load and accumulation of mercury in tissues is the release of mercury vapour from amalgam fillings.

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26. Olsson, S; Bergman, M.: Daily Dose Calculations from Measurements of Intra-oral Mercury Vapor. J Dent Res. 71(2):414-23. Feb 1992.

ABSTRACT: Measurements of intra-oral mercury vapor from amalgam fillings are discussed. It was shown that the only quantity which it is possible to measure is the mercury release rate, and that the concentrations of mercury vapor in the oral cavity published in most earlier studies are the mercury concentrations in the measuring cell of the measuring apparatus and not the concentrations in the oral cavity. The consequences for the daily dose equations of the facts that the mercury source is present inside the oral cavity and that the amount of mercury released during a certain time is limited are discussed. It was found that most daily dose equations used have a questionable mercury distribution on inspiration, expiration, and swallowing. Re-calculations of almost all the available daily dose data showed a mean daily dose value of about 1.3 micrograms Hg/day (range, 0.3-2.2 micrograms Hg/day). The mean swallowed amount of mercury from intra-oral mercury vapor was calculated as being in the order of 10 micrograms Hg/day (range, 2.4-17 micrograms Hg/day), resulting in an estimated absorption of about 1 microgram Hg/day from the gastro-intestinal tract.

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27. Oral Surg Oral Med Oral Pathol (1990 Jul) 70(1):55-8

ABSTRACT: A total of 49 consecutive patients with lesions of the oral mucosa that were in contact with corroding dental amalgam restorations were subdivided into two groups. In group 1 the lesions were restricted to the contact area opposing the dental restoration, whereas the extent of the lesions in group 2 exceeded that of the contact area. Epicutaneous test for mercury allergy showed that a significantly greater proportion of the patients in group 1 had positive reactions to mercury than in group 2 (p = 0.019). The amalgam restorations were replaced by composite resin or porcelain fused to gold crowns, or contact between amalgam fillings and oral mucosa was prevented by an acrylic splint. After this treatment regression of lesions was far more pronounced in group 1 than in group 2 (p less than 0.001). On the basis of these findings, contact allergy to mercury is suggested as a possible etiologic factor of the mucosal changes in group 1, and the designation contact lesion is proposed for such lesions. The lesions of patients in group 2 seem unrelated to a contact allergy to mercury, and other causes such as lichen planus should be considered

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28. Oskarsson, A; Schultz, A; Skerfving, S; Hallen, IP; Ohlin, B; Lagerkvist, BJ. Total and Inorganic Mercury in Breast Milk in Relation to Fish Consumption and Amalgam in Lactating Women. Arch Environ Health, 51(3):234-41, 1996.

ABSTRACT: Total mercury concentrations (mean standard deviation) in breast milk, blood, and hair samples collected 6 wk after delivery from 30 women who lived in the north of Sweden were 0.6 + 0.4 ng/g (3.0 + 2.0 nmoVkg), 2.3 _ 1.0 ng/g (11.5 _ 5.0 nmoVkg), and 0.28 _ 0.16 microg/g (1.40 + 0.80 micromoVkg), respectively.

The results indicated that there was an efficient transfer of inorganic mercury from blood to miIk and that, in this population, mercury from amalgam fillings was the main source of mercury in milk. Exposure of the infant to mercury from breast milk was calculated to range up to 0.3 microg/kg x d, of which approximately one-half was inorganic mercury. This exposure, however, corresponds to approximately one-half the tolerable daily intake for adults recommended by the World Health Organization. We concluded that efforts should be made to decrease mercury burden in fertile women.

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29. Pendergrass, JC; Haley, BE; Vimy, MJ; Winfield, SA; Lorscheider, FL. Neurotoxicology Mercury Vapour Inhalation Inhibits Binding of GTP to Tubulin in Rat Brain: Similarity to a Molecular Lesion in Alzheimer Diseased Brain., In Press (June-July), 1997.

ABSTRACT: Hg2+ interacts with brain tubulin and disassembles microtubules that maintain neurite structure. Since it is well known that Hg Vapour ( HgO) is continuously released from "silver" amalgam tooth fillings and is absorbed into brain, rats were exposed to Hg 4 h/day for 0, 2, 7, 14 and 28 d at 250 or 300 ug Hg/m3 air, concentrations present in mouth air of some humans with many amalgam fillings. Average rat brain Hg concentrations increased significantly (11-47 fold) with duration of Hg exposure. By 14 d Hg exposure, photoaffinity labeling of the betasubunit of the tubulin dimer with [alpha32P]8N3GTP in brain homogenates was decreased 41-74%, upon analysis of SDS-PAGE autoradiograms. The identical neurochemical lesion of similar or greater magnitude is evident in Alzbeimer brain homogenates from approximately 80% of patients, when compared to human age-matched neurological controls. Total tubulin protein levels remained relatively unchanged between Hg exposed rat brains and controls, and between Alzheimer brains and controls. Since the rate of tubulin polymerisation is dependent upon binding of GTP to tubulin dimers, we conclude that chronic inhalation of low-level Hg can inhibit polymerisation of brain tubulin essential for formation of microtubules.


30. Pendergrass, J; Israel, M; Haley, B The Deleterious Effects of Low Micromolar Mercury on Important Brain and Cerebrospinal Fluid Proteins.. American Association of Pharmaceutical Scientists, Annual Meeting,5-9 November 1995, Miami, Florida.

ABSTRACT: Alzheimer's Disease (AD) is the most common cause of adult onset dementia. There is no effective treatment or proven diagnostic indicator for AD. While the etiology and pathogenesis of AD are not known, there have been several published reports of altered protein-nucleotide interactions. Our laboratory developed the technique of nucleotide photoaffinity labeling as a method for identifying the nucleotide binding domains of several important enzymes. We have also shown this technique to be a very sensitive and reliable tool for identifying changes in nucleotide-proteins interactions when comparing AD brain and CSF (cerebrospinal fluid) to non- demented control tissues. For example, we have shown using 32P8N3GTP and 32P8N3ATP that b-tubulin and creatine kinase (CK) interactions, respectively, are aberrant in AD brain homogenates relative to age-matched neurologic controls. This is despite both proteins being present near control levels, indicating that both tubulin and CK have been modified in the disease state. Currently, photolabeling technology coupled with high resolution 2-D gels (IEF X SDS-PAGE) has been developed to enhance the ability to detect changes in protein-nucleotide interactions in brain and CSF samples. This approach shows what appears to be specific changes in the 32P8N3ATP photolabeling profile of 2D separated CSF proteins of AD patients versus those of non-demented control CSFs or in CSF of other neurodegenerative diseases. This technology also shows that exposure of human control brain homogenates to 1-3 microM Hg2+EDTA complex produces 32P8N3GTP-b-tubulin interactions comparable to tbat of AD brains.

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31. Reinhardt JW Side-effects: mercury contribution to body burden from dental amalgam. Adv Dent Res (1992 Sep) 6:110-3

ABSTRACT: The purpose of this paper is to examine and report on studies that relate mercury levels in human tissues to the presence of dental amalgams, giving special attention to autopsy studies. Until recently, there have been few published studies examining the relationship between dental amalgams and tissue mercury levels. Improved and highly sensitive tissue analysis techniques have made it possible to measure elements in the concentration range of parts per billion. The fact that mercury can be absorbed and reach toxic levels in human tissues makes any and all exposure to that element of scientific interest. Dental amalgams have long been believed to be of little significance as contributors to the overall body burden of mercury, because the elemental form of mercury is rapidly consumed in the setting reaction of the restoration. Studies showing measurable elemental mercury vapor release from dental amalgams have raised renewed concern about amalgam safety. Mercury vapor absorption occurs through the lungs, with about 80% of the inhaled vapor being absorbed by the lungs and rapidly entering the bloodstream. Following distribution by blood circulation, mercury can enter and remain in certain tissues for longer periods of time, since the half-life of excretion is prolonged. Two of the primary target organs of concern are the central nervous system and kidneys.

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32. Retrograde Axonal Transport of Mercury in Primary Sensory Neurons Innervating the Tooth Pulp in the Rat. Neurosci Lett. 115(1):29-32. Jul 17, 1990.

ABSTRACT: The pulp cavity of the first upper molar was exposed unilaterally in adult rats with a dental drill and about 1 microliter of mercuric chloride was injected into the coronal pulp. The rats were sacrificed after 1-24 days and frozen sections from the trigeminal ganglia were subjected to silver acetate autometallography for demonstration of mercury. Mercury was found to have accumulated in neurons of the ipsilateral trigeminal ganglion by retrograde axonal transport. The possible implications of this finding are discussed.

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33. Sato, K; Kusada, Y; Zhangihiro, H; Ishii, Y; Mori, T; Hirai, T; Yomiyama, T; Iida, K An Epidemiological Study of Mercury Sensitization.. Allergology International, 46:201-6, 1997.

ABSTRACT: Mercury sensitization has been historically in question and may be related to recent increases of type I allergic diseases. To clarify the epidemiological factors of mercury sensitization, we investigated factors relating to mercury sensitization in 215 medical students. Their allergic symptoms, family histories and lifestyles were studied by questionnaire. Patch tests were performed with HgC12 (0.05% aq.) And NiSO4 (5% aq.). AntiDermatophagoides and anti-Cryptomeria pollen IgE antibodies in sera were also measured. Urinary mercury concentrations were measured in 25 mercury sensitised and 44 non-sensitized subjects (controls). Hair mercury concentrations were also measured in 19 sensitised and 22 non-sensitized subjects. While the positive rate of nickel was 6.0% (13/215), that of mercury was high (13%, 28/215). The subjects' individual histories of allergic rhinitis, eczema, urticaria and allergic conjunctivitis were significantly associated with family histories of these conditions (P. P and P. respectively), as reported in the literature. However, no allergenspecific antibody positivity or past history of allergic disease was associated with mercury sensitization. Mercury sensitised subjects had experienced eczema, caused by cosmetics, shampoos, soaps and hair creams significantly more frequently (P). The history of mercurochrome usage was not associated with mercury sensitization. The number of teeth treated with metals in mercury sensitized subjects was significantly higher than that in the control group (6.8 +/- 4.3 vs 4.8 +/- 1, P). There were significant differences in urinary mercury concentrations (specific gravity adjusted levels) between mercury sensitised subjects and non-sensitized subjects (2.0 +/- 0.9 and 1.3 +/- 0.6 mcg/L respectively; P). There were also significant differences in hair mercury concentrations between mercury sensitised and non-sensitized subjects (2.0 +/- 0.9 and 1.2 +/- 0.5 mcg/g respectively; P). These results suggest that mercury sensitization is associated with exposure to mercury in the living environment and that skin symptoms are possibly associated as preceding factors.

ASOMAT COMMENT: The finding of 13.0% allergic to mercury is very important, especially combined with the finding that the subjects with amalgam fillings had significantly higher levels of mercury allergy. The authors even stated (page 205): "If the use of amalgams was to be limited, the prevalence of Hg sensitization would be expected to lessen." This is yet another controlled study demonstrating a high incidence of allergy to mercury. In sixteen years of investigation, we have yet to find one single controlled study supporting the position of organized dentistry that allergy to mercury is "very rare", "one in a million", "less than 1%", or any other vague, unsupportable level! Continued public promotion of these unsupportable statements by health professionals could constitute negligent misrepresentation.

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34. Shimojo N; Arai Y. Effects of exercise training on the distribution of metallic mercury in mice. Hum Exp Toxicol. 13(8):524-528, Aug 1994.

ABSTRACT: 1. The purpose of this study was to correlate exercise induced changes of antioxidant enzymes with the distribution of mercury after mercury vapour exposure in mice.

2. Exercise training consisted of swimming (1h/day for 5 days/week) for 9 weeks. After 9 weeks of training, swim-trained mice showed significantly elevated levels of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSHpx) in their red blood cells, CAT and GSHpx in their kidneys and SOD in the liver.

3. Exercised mice (EX) and non-exercised mice (N.Ex) were exposed to mercury vapour (3.5 mg m3) for 1 hour. Mercury concentrations were assayed in the blood, brain, heart, lungs, liver and kidneys along with the mercury content of the entire body. The whole body mercury content showed no significant difference in any measurement (immediately, 24 h and 48 h. After mercury exposure) between the Ex and N.Ex groups. Mercury concentrations in the Ex group were significantly higher than the N.Ex group in the heart, whole blood, red blood cells and the brain at 25 and 49 h; and in the plasma and kidneys at 24 h. 4. It was concluded that exercise training is a factor in distribution changes of mercury after exposure to mercury vapour, though it is not a factor in the total absorption and excretion of mercury.

ASOMAT COMMENT: If extrapolated to humans, it would indicate that individuals with a mouth full of amalgams, who exercise, are at much greater risk of heart disease and mental illness than individuals who are mercury-free performing the same degree of exercise.

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35. Siblerud RL The relationship between mercury from dental amalgam and the cardiovascular system. Sci Total Environ (1990 Dec 1) 99(1-2):23-35

ABSTRACT: The findings presented here suggest that mercury poisoning from dental amalgam may play a role in the etiology of cardiovascular disorders. Comparisons between subjects with and without amalgam showed amalgam- bearing subjects had significantly higher blood pressure, lower heart rate, lower hemoglobin, and lower hematocrit. Hemoglobin, hematocrit, and red blood cells were significantly lower when correlated to increased levels of urine mercury. The amalgam subjects had a greater incidence of chest pains, tachycardia, anemia, fatigue, tiring easily, and being tired in the morning. The data suggest that inorganic mercury poisoning from dental amalgam does affect the cardiovascular system.

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36. Stejskal V, Forsbeck M, Cederbrant K E, Asteman O J of Clin Immun, Vol. 16, No.1, 1996, pp. 31-40.

ABSTRACT: This paper investigates the hypothesis that mercury from silver dental fillings (amalgam) may be related to multiple sclerosis (MS). It compares blood findings between MS subjects who had their amalgams mercury could be causing the pathological and physiological changes found in multiple sclerosis.

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37. Summers AO Wireman J Vimy MJ Lorscheider FL Marshall B Levy SB Bennett S Billard L Mercury released from dental "silver" fillings provokes an increase in mercury- and antibiotic-resistant bacteria in oral and intestinal floras of primates Antimicrob Agents Chemother (1993 Apr) 37(4):825-34

ABSTRACT: In a survey of 640 human subjects, a subgroup of 356 persons without recent exposure to antibiotics demonstrated that those with a high prevalence of Hg resistance in their intestinal floras were significantly more likely to also have resistance to two or more antibiotics. This observation led us to consider the possibility that mercury released from amalgam ("silver") dental restorations might be a selective agent for both mercury- and antibiotic-resistant bacteria in the oral and intestinal floras of primates. Resistances to mercury and to several antibiotics were examined in the oral and intestinal floras of six adult monkeys prior to the installation of amalgam fillings, during the time they were in place, and after replacement of the amalgam fillings with glass ionomer fillings ( in four of the monkeys). The monkeys were fed an antibiotic-free diet, and fecal mercury concentrations were monitored. There was a statistically significant increase in the incidence of mercury-resistant bacteria during the 5 weeks following installation of the amalgam fillings and during the 5 weeks immediately following their replacement with glass ionomer fillings. These peaks in incidence of mercury-resistant bacteria correlated with peaks of Hg elimination (as high as 1 mM in the feces) immediately following amalgam placement and immediately after replacement of the amalgam fillings. Representative mercury-resistant isolates of three selected bacterial families (oral streptococci, members of the family Enterobacteriaceae, and enterococci) were also resistant to one or more antibiotics, including ampicillin, tetracycline, streptomycin, kanamycin, and chloramphenicol. While such mercury- and antibiotic- resistant isolates among the staphylococci, the enterococci, and members of the family Enterobacteriaceae have been described, this is the first report of mercury resistance in the oral streptococci. Many of the enterobacterial strains were able to transfer mercury and antibiotic resistances together to laboratory bacterial recipients, suggesting that the loci for these resistances are genetically linked. Our findings indicate that mercury released from amalgam fillings can cause an enrichment of mercury resistance plasmids in the normal bacterial floras of primates. Many of these plasmids also carry antibiotic resistance, implicating the exposure to mercury from dental amalgams in an increased incidence of multiple antibiotic resistance plasmids in the normal floras of nonmedicated subjects.

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38. Szucs, A; Angiello, C; Salanki, J; Carpenter, DO. Effects of Inorganic Mercury and Methylmercury on the Ionic Currents of Cultured Rat Hippocampal Neurons. Cell Mol Neurobiol, 17(3):273-88, 1997.

ABSTRACT: 1. The effects of inorganic Hg2+ and methylmercuric chloride in the ionic currents of cultured hippocampal neurons were studied and compared. We examined the effects of acute exposure to the two forms of mercury on the properties of voltage activated Ca2+ and Na+ currents and N- methyl-D-aspartate (NMDA)-induced currents. 2. High-voltage activated Ca2+currents (L-type) were inhibited by both compounds at low micromolar concentrations in an irreversible manner. Mercuric chloride was five times as potent as methyl mercury in blocking L- channels. 3. Both compounds caused a transient increase in the low-voltage activated (T-type) currents at low concentrations (1 microM) but blocked at higher concentrations and with longer periods of time. 4. Inorganic mercury blockade was partially use dependent, but that by methyl mercury was not. There was no effect of exposure of either form of mercury on the I-V characteristics of Ca2+ currents. 5. Na(+)and NMDA- induced currents were essentially unaffected by either mercury compound, showing only a delayed nonspecific effect at a time of overall damage of the membrane. 6. We conclude that both mercury compounds show a relatively selective blockade of Ca'+ currents, but inorganic mercury is more potent than methyl mercury.

ASOMAT COMMENT: This is additional evidence that inorganic mercury (Hg2 +) can now be considered at least as toxic as is methyl mercury, and probably more so. The confusion results from a lack of knowledge about the toxicokinetics of various forms of mercury. If exposure is to inorganic mercury (i.e., mercuric chloride), less mercury reaches the tissues due to the poor absorption rate. Methyl mercury has been found to be very toxic because of its high absorption rate (gastrointestinally by ingestion). Now, it has become clear that mercury vapor (HgO) is extremely toxic because of its high absorption rate by inhalation into the blood and by transmembrane penetration into cells, where it is oxidised into inorganic mercury ions ( Hg2+).

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39. Vanherle G Dental care using silver amalgam] Verh K Acad Geneeskd Belg (1996) 58(5):587-634

ABSTRACT: Dental amalgam is the most widely used filling material in dentistry. In our country there are an estimated 40 million amalgam fillings in place. The mercury present in these fillings has caused health concerns over the last 160 years that amalgam has been used in decayed teeth. The fears have always proven to be unjustified and no harmful effects have ever been demonstrated in dental patients. Mercury can be found in several forms. In dentistry, only the metallic form is used, while inorganic and organic compounds are also present in the environment. The metallic form is absorbed in the human body mostly through the lungs. Once mercury reaches toxic levels inside the body, it will interfere with cell metabolism. Most important among the target organs are the brain, the liver and the kidneys.

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40. Vimy MJ Lorscheider FL Serial measurements of intra-oral air mercury: estimation of daily dose from dental amalgam : J Dent Res (1985 Aug) 64(8):1072-5

ABSTRACT: Serial measurements of Hg concentration in intra-oral air were made during and after chewing stimulation in 35 subjects with occlusal amalgam restorations. Hg concentrations remained elevated during 30 min of continuous chewing and declined slowly over 90 min after cessation of chewing. By curve-fitting and integration analysis of data during these time periods (including corrections for respiratory volume, retention rate of inspired Hg, oral-to-nasal breathing ratios, and consumption of three meals and three snacks per day), we calculated that all subjects received an average daily Hg dose of approximately 20 micrograms. Subjects with 12 or more occlusal amalgam surfaces were estimated to receive a daily Hg dose of 29 micrograms, whereas in subjects with four or fewer occlusal amalgam surfaces, the dose was 8 micrograms. These Hg dosages from dental amalgam were as much as 18-fold the allowable daily limits established by some countries for Hg exposure from all sources in the environment. The results demonstrate that the amount of elemental Hg released from dental amalgam exceeds or comprises a major percentage of internationally accepted threshold limit values for environmental Hg exposure. It is concluded that dental amalgam Hg makes a major contribution to total daily dose.

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41. Vimy M.J. and Lorscheider F.L. Dental amalgam mercury daily dose estimated from intra-oral vapor measurements: A predictor of mercury accumulation in human tissues The Journal of Trace Elements in ExDerimental Medicine 3:1 11-123. 1990.

ABSTRACT: Recent misconceptions regarding Hg exposure from dental amalgams have been based on several questionable assumptions. The present paper reexamines earlier estimations of Hg daily dose from dental amalgam in order to elaborate and refine the mechanical and volumetric parameters of open-mouth Hg vapor sampling. This facilitates a comparison with the physiological parameters of human respiration. Corrections for the sampling factors of flow rate and sampling dilution, and the respiratory factor of Hg accumulation in the closed mouth between oral inhalations, reduce our original daily dose estimates by approximately 50%. Application of a general pharmacokinetic model with our revised Hg daily dose estimates results in predictions for brain, kidney, blood, and urine which approximate tissue Hg measurements reported in subjects with dental amalgams. When tissue Hg predictions are made based upon alternate Hg daily dose estimates proposed by other investigators, the resultant error was as much as 11-fold lower than were actual tissue measurements in humans. It is concluded that intra-oral air Hg vapor measurements can be useful for estimating Hg daily dose and tissue Hg levels. (Address reprint requests to Dr. F.L. Lorscheider, Dept. Medical Physiology, Faculty of Medicine, University of Calgary, 3330 Hospital Drive N.W., Calgary, Alberta, Canada T2N 4N1.)

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42. Weiner-JA; Nylander-M; Berglund-F Does mercury from amalgam restorations constitute a health hazard? AU: AD: National Board of Occupational Safety and Health, Solna, Sweden. Sci-Total-Environ. 1990 Dec 1; 99(1-2): 1-22

ABSTRACT: Amalgam is the most extensively used implant material in dentistry. There have been no clinical trials of this substance and there are no epidemiological studies that allow any conclusions on the safety of amalgam fillings. Amalgam restorations continuously emit mercury vapour, which is absorbed in considerable quantities via the lungs. A comparison with dose-effect relationships, obtained in occupational studies, for certain effects on the kidneys and central nervous system (CNS), suggests that individuals with unusually high emission of mercury from amalgam fillings are at risk. It is unclear whether or not clinically significant effects could be expected. The limited sensitivity of available occupational studies, together with insufficient knowledge of possible host factors affecting resistance to mercury, implies that other more severe effects in susceptible individuals cannot be excluded. Information on long-term effects on organs other than brain or kidney is sparse. Animal studies suggest the possibility of immune system reactions to mercury, i.e. development of autoimmunity, that are not primarily dose- dependent, but rather depend on genetic susceptibility. From a toxicological point of view, amalgam is an unsuitable material for dental restorations.

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43. Weiner-JA; Nylander-M The relationship between mercury concentration in human organs and different predictor variables. National Board of Occupational Safety and Health, Solna, Sweden. Sci-Total-Environ. 1993 Sep 30; 138(1-3): 101-15

ABSTRACT: Samples from different tissues were collected from autopsies of individuals of the general population of the Stockholm area, Sweden. The samples were analysed for total mercury content using radiochemical neutron activation analysis. Average concentrations of mercury in occipital cortex, abdominal muscle, pituitary gland and kidney cortex were, 10.6 (2.4-28.7), 3.3 (0.9-5.4), 25.0 (6.3-77) and 229 (21.1-810) micrograms/kg wet weight, respectively. Possible predictor variables for mercury concentrations were tested in multiple linear regression models. An effect of a number of tooth surfaces with amalgam was seen in occipital lobe cortex, abdominal muscle and pituitary gland, but not in kidney cortex. In occipital lobe cortex and abdominal muscle, concentrations of mercury increased with age. Explanations discussed include: that a significant fraction of the mercury retained from amalgam fillings has a very long biological half-life; a decreasing capacity of mercury excretion with age; or higher fish consumption in the older individuals.

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44. Wenstrup D; Ehmann WD; Markesbery WR; Trace element imbalances in isolated subcellular fractions of Alzheimer's disease brains. Department of Chemistry, University of Kentucky, Lexington. Brain Res, 533: 1, 1990 Nov 12, 125-31

ABSTRACT: Concentrations of 13 trace elements (Ag, Br, Co, Cr, Cs, Fe, Hg, K, Na, Rb, Sc, Se, Zn) in isolated subcellular fractions (whole brain, nuclei, mitochondria, microsomes) of temporal lobe from autopsied Alzheimer's disease (AD) patients and normal controls were determined utilizing instrumental neutron activation analysis. Comparison of AD and controls revealed elevated Br (whole brain) and Hg (microsomes) and diminished Rb (whole brain, nuclear and microsomes), Se (microsomes) and Zn (nuclear) in AD. The elevated Br and Hg (Mercury) and diminished Rb are consistent with our previous studies in AD bulk brain specimens. Comparison of element ratios revealed increased Hg/Se, Hg/Zn and Zn/Se mass ratios in AD. Se and Zn play a protective role against Hg toxicity and our data suggest that they are utilized to detoxify Hg in the AD brain. Overall our studies suggest that Hg could be an important toxic element in AD.

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45. Wojciechowski, J; Kowalski, W. Cardiac and Aortic Lesions in Chronic Experimental Poisoning With Mercury Vapors. Pol Med Sci Hist Bull., 15(2):255-60, Mar 1975.

ABSTRACT: The nature of the toxic influence of mercury and its effect on the cardiovascular system are not well understood. In chronic poisoning with metallic mercury and its compounds, circulatory disorders have been observed in patients. The problem whether metallic mercury damages the endocardium and myocardium directly or indirectly through vascular changes or vegetative system stimulation remains unsolved. A study was undertaken in which a group of experimental rabbits was exposed to the chronic action of mercury vapors by inhalation and compared with a control group. Before the experiment and towards its end, ECG were taken and 24-hr urinary excretion of mercury was determined in both groups. After 3 months the animals were autopsied, and fragments of myocardium, papillary muscles, endocardium and ascending aorta were taken for histopathologic investigation. In the poisoned animals, the ECG tracings showed bradycardia. Morphologic lesions had the character of thrombosis in small and medium caliber blood vessels, necrotic foci, thickening of the endocardium of the papillary muscles and perivalvular region and endothelial proliferation with inflammatory foci. The results indicate that, besides influencing the vegetative system, mercury vapor damages the endocardium directly and produces vascular lesions resulting in myocardial changes.

 

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