Mercury

“Sixty consecutive patients who had undergone replacement of dental amalgam fillings and a protocol of nutritional support and heavy metal detoxification using dimercapto-propanyl-sulfate and neural therapy were surveyed. A questionnaire was mailed to the patients and 42 responded, resulting in a response rate of 70%. The reasons for undergoing treatment were many, ranging from a patient’s desire to avoid potential health problems in the future to treatment of serious current disease. Although medical diagnoses were made when possible before treatment, this survey studied only the patients’ estimations of their most distressing symptoms and their evaluations of response to treatment. The most common complaints were problems with memory and/or concentration; muscle and/or joint pain; anxiety and insomnia; stomach, bowel, and bladder complaints; depression; food or chemical sensitivities; numbness or tingling; and eye symptoms, in descending order of frequency. The most distressing symptoms were headache and backache, fatigue, and memory and concentration problems. Headache and backache responded best to treatment, but all symptoms showed considerable improvement on average. Of the respondents, 78% reported that they were either satisfied or very satisfied with the results of treatment, and 9.5% reported that they were disappointed.”

We report 2 cases of relapsing nummular dermatitis according to mercury sensitivity, which was confirmed by patch testing. Removal of the amalgam from dental metal alloys markedly improved their skin eruptions. One of the patients, a dentist, experienced exacerbation of the eruptions on his lower legs after handling dental amalgam. Hypersensitivity to haptens such as metals is possibly involved in, at least in some patients, the pathogenesis of nummular dermatitis.

“OBJECTIVE:
Thimerosal is an important preservative in vaccines and ophthalmologic preparations. The substance is known to be a type IV sensitizing agent. High sensitization rates were observed in contact-allergic patients and in health care workers who had been exposed to thimerosal-preserved vaccines. There is evidence for the involvement of the glutathione system in the metabolism of thimerosal or its decomposition products (organomercury alkyl compounds). Thus detoxification by polymorphically expressed glutathione S-transferases such as GSTT1 and GSTM1 might have a protective effect against sensitization by these substances.

METHODS:
To address this question, a case control study was conducted, including 91 Central European individuals with a positive patch-test reaction to thimerosal. This population was compared with 169 healthy controls and additionally with 114 individuals affected by an allergy against para-substituted aryl compounds. The latter population was included in order to test whether possible associations were due to substance-specific effects, or were a general feature connected with type IV immunological diseases. Homozygous deletions of GSTT1 and GSTM1 were determined by polymerase chain reaction.

RESULTS:
Glutathione S-transferase M1 deficiency was significantly more frequent among patients sensitized to thimerosal (65.9%, P = 0.013) compared with the healthy control group (49.1%) and the “para-compound” group (48%, P = 0.034). Glutathione S-transferase T1 deficiency in the thimerosal/mercury group (19.8%) was barely elevated versus healthy controls (16.0%) and the “para-compound” group (14.0%). The combined deletion (GSTT1-/GSTM1-) was markedly more frequent among thimerosal-sensitized patients than in healthy controls (17.6% vs. 6.5%, P = 0.0093) and in the “para-compound” group (17.6% vs. 6.1%, P =0.014), revealing a synergistic effect of these enzyme deficiencies (healthy controls vs. thimerosal GSTM1 negative individuals, OR = 2.0 [CI = 1.2-3.4], GSTT1-, OR = 1.2 [CI = 0.70-2.1], GSTM1/T1-, OR = 3.1 [CI = 1.4-6.5]).

CONCLUSIONS:
Since the glutathione-dependent system was repeatedly shown to be involved in the metabolism of thimerosal decomposition products, the observed association may be of functional relevance.”

“The aim of this investigation was to establish mercury (Hg) health effects on dentists and dental assistants, its relationship with exposure conditions and the potential renal damage Hg-related. The total population was 66 people, with a sample of 37 (56%), 22 dentists (59.5%, 19 male, 3 female) and 15 dental assistants (40.5%, all female). This was accomplished by an interview, Hg in urine (Hg-U) and N-acetyl-B-D-glucosaminidase activity in urine (NAG-U). Average values of Hg-U for dentists were 22.4 +/- 6.4 micrograms/g creatinine and 22.2 +/- 6.1 micrograms/g creatinine for dental assistants NAG-U average values were 2.9 +/- 3 U/L and 5.2 +/- 8.1 U/L respectively. There were no statistically significant differences between these averages (p > 0.05). There was no correlation between the quantity of amalgam prepared and working hours with Hg-U and NAG-U. Most frequent symptoms referred by dentists were: irritability (54.5%), cephalalgia (45.4%), arthralgias (40.9%), and the ones more referred by assistants were arthralgias (53.3%), irritability (46.7%) and cephalalgia (46.7%). It was not found a significative risk of having them among these groups. There is a need for further investigations including environmental monitoring of Hg, clinical evaluation and neurobehavioural tests to detect early effects. It is important to enforce personal safety measures to control the exposure.”

“The effects of thimerosal, a sulfhydryl oxidizing agent, on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) sodium channels in rat dorsal root ganglion neurons were studied using the whole-cell patch clamp technique. Thimerosal blocked the two types of sodium channels in a dose-dependent manner. The inhibitory effect of thimerosal was much more pronounced in TTX-R sodium channels than TTX-S sodium channels. The effect of thimerosal was irreversible upon wash-out with thimerosal-free external solution. However, dithiothreitol, a reducing agent, partially reversed it. Thimerosal shifted the steady-state inactivation curves for both types of sodium channels in the hyperpolarizing direction. The voltage dependence of activation of both types of sodium channels was shifted in the depolarizing direction by thimerosal. The inactivation rate in both types of sodium channels increased after thimerosal treatment. All these effects of thimerosal would add up to cause a depression of sodium channel function leading to a diminished neuronal excitability.”

“Concentrations of heavy metals, including mercury, have been shown to be altered in the brain and body fluids of Alzheimer’s disease (AD) patients. To explore potential pathophysiological mechanisms we used an in vitro model system (SHSY5Y neuroblastoma cells) and investigated the effects of inorganic mercury (HgCl2) on oxidative stress, cell cytotoxicity, beta-amyloid production, and tau phosphorylation. We demonstrated that exposure of cells to 50 microg/L (180 nM) HgCl2 for 30 min induces a 30% reduction in cellular glutathione (GSH) levels (n = 13, p<0.001). Preincubation of cells for 30 min with 1 microM melatonin or premixing melatonin and HgCl2 appeared to protect cells from the mercury-induced GSH loss. Similarly, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assays revealed that 50 microg/L HgCl2 for 24 h produced a 50% inhibition of MTT reduction (n = 9, p<0.001). Again, melatonin preincubation protected cells from the deleterious effects of mercury, resulting in MTT reduction equaling control levels. The release of beta-amyloid peptide (Abeta) 1-40 and 1-42 into cell culture supernatants after exposure to HgCl2 was shown to be different: Abeta 1-40 showed maximal (15.3 ng/ml) release after 4 h, whereas Abeta 1-42 showed maximal (9.3 ng/ml) release after 6 h of exposure to mercury compared with untreated controls (n = 9, p<0.001). Preincubation of cells with melatonin resulted in an attenuation of Abeta 1-40 and Abeta 1-42 release. Tau phosphorylation was significantly increased in the presence of mercury (n = 9, p<0.001), whereas melatonin preincubation reduced the phosphorylation to control values. These results indicate that mercury may play a role in pathophysiological mechanisms of AD.”

“Our objective was to describe the occurrence of musculoskeletal symptoms and how they affect the daily life of three different occupational groups of dental personnel. A cross sectional-study was performed among 268 dental staff members and 111 referents. Female dental hygienists and female dentists showed, compared with their referents, higher prevalence of symptoms during the past 12 months from neck, shoulders and hands/wrists. Both dental groups also had higher frequencies of combined symptoms from these body regions, as well as longer duration of symptoms in neck and shoulders during the past 12-month period. Male dentists had higher frequencies of neck and shoulder symptoms compared with their referents. Female dental assistants did not deviate from their referents. The symptoms from each single body region, or the occurrence of symptoms from multiple regions in a subject, did not show any statistically significant association with mercury (whole blood and urinary levels) or selenium (plasma level) status, neither with smoking habits nor overweight (Body Mass Index). The high frequency of musculoskeletal disorders probably reflects the specific work load in dentistry, with high demands on vision and precision and fine manipulative hand movements and work with unsupported, elevated arms. The symptoms might impair work capacity and the future possibility to stay in the profession. Further studies are needed to verify this.”

In 29 volunteers with a low amalgam load, the number of amalgam-covered tooth surfaces and the occlusal area of the fillings were determined. Before and at select times after removal of all amalgams, concentrations of total mercury were measured by cold-vapor atomic absorption in plasma and erythrocytes as well as in urine together with the excretion rate. Absorbed daily doses were estimated from intraoral Hg emission by two separate methods. The transfer of Hg from the fillings via the oral cavity and blood to urinary excretion was evaluated according to the most representative combination of parameters. This consisted of occlusal area (1), absorbed dose (2), Hg concentration in plasma (3) and urinary excretion (4). Pairwise correlation coefficients were 0.49 for parameters 1 vs. 2, and 0.75 each for parameters 2 vs. 3 and 3 vs. 4. Within 9 days after removal of the fillings, a transient increase in Hg levels was observed in plasma only; in the group without a rubber dam, concentrations increased significantly above pre-removal values at days 1 and 3, whereas they decreased significantly below pre-removal values at day 30 in the rubber-dam group and at day 100 in both groups. Excretion rates decreased significantly at day 100 in the protected group. Peak plasma-Hg was 0.6 ng/ml on average at day 1 and decreased with halftimes of 3 and 43 days in subjects protected by a rubber dam. The results indicated that concentrations of total mercury in plasma responded rapidly to changes in the amalgam status and reflected the actual absorption most reliably. Notably, plasma-Hg levels were sensitive enough to detect a transient attenuation of the additional exposure after using a rubber dam during the removal of only a few fillings. However, being small in magnitude and lasting 100 days at best, the rubber-dam effect had minor toxicological relevance.

“Cells respond to physiologic stress by enhancing the expression of specific stress proteins. Heat-shock proteins (hsps) and glucose-regulated proteins (grps) are members of a large superfamily of proteins collectively referred to as stress proteins. This particular stress-protein response has evolved as a cellular strategy to protect, repair, and chaperone other essential cellular proteins. The objective of this study was to evaluate the differential expression of four hsps in the renal cortex and medulla during experimental nephrotoxic injury using HgCl2. Male Sprague-Dawley rats received single injections of HgCl2 (0.25, 0.5, or 1 mg Hg/kg, i.v.). At 4, 8, 16, or 24 h after exposure, kidneys were removed and processed for histopathologic, immunoblot, and immunohistochemical analyses. Nephrosis was characterized as minimal or mild (cytoplasmic condensation, tubular epithelial degeneration, single cell necrosis) at the lower exposures, and progressed to moderate or severe (nuclear pyknosis, necrotic foci, sloughing of the epithelial casts into tubular lumens) at the highest exposures. Western blots of renal proteins were probed with monoclonal antibodies specific for 4 hsps. In whole kidney, Hg(II) induced a time- and dose-related accumulation of hsp72 and grp94. Accumulation of hsp72 was predominantly localized in the cortex and not medulla, while grp94 accumulated primarily in the medulla but not cortex. The high, constitutive expression of hsp73 did not change as a result of Hg(II) exposure, and it was equally localized in cortex and medulla. Hsp90 was not detected in kidneys of control or Hg-treated rats. Since hsp72 has been shown involved in cellular repair and recovery, and since Hg(II) damage occurs primarily in cortex, we investigated the cell-specific expression of this hsp. Hsp72 accumulated primarily in undamaged distal convoluted tubule epithelia, with less accumulation in undamaged proximal convoluted-tubule epithelia. These results demonstrate that expression of specific stress proteins in rat kidney exhibits regional heterogeneity in response to Hg(II) exposure, and a positive correlation exists between accumulation of some stress proteins and acute renal cell injury. While the role of accumulation of hsps and other stress proteins in vivo prior to or concurrent with nephrotoxicity remains to be completely understood, these stress proteins may be part of a cellular defense response to nephrotoxicants. Conversely, renal tubular epithelial cells that do not or are unable to express stress proteins, such as hsp72, may be more susceptible to nephrotoxicity.”

“OBJECTIVE:

To study the Streptococcus mutans in the plaque on the surface of amalgam fillings on the conversion of inorganic mercury to organic mercury.

METHODS:

Plaque was sampled from the amalgam restorations after amalgam filling regularly, serving the unfilled tooth as control. Streptococcus mutans was identified and inoculated to 10 ml TSB. After incubated 24 hours, mercury in water was added to the concentration of 100 ng/ml, incubated 24 hours again, the concentration of inorganic and organic mercury was determined.

RESULTS:

It was found that the difference of organic mercury and organic mercury between the baseline and the times after amalgam filling in test group and control was significant, while the difference between the times after amalgam filling was not significant, and the difference between the test group and the control was not significant, either.

CONCLUSION:

Streptococcus mutans can convert inorganic mercury to organic mercury in some way, and the mercury of amalgam plays some role in it.”